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Journal articles on the topic 'Pyrogene'
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1
Nakagawa, Yukari, Hideko Maeda, and Toshimi Murai. "Evaluation of the In Vitro Pyrogen Test System Based on Proinflammatory Cytokine Release from Human Monocytes: Comparison with a Human Whole Blood Culture Test System and with the Rabbit Pyrogen Test." Clinical and Vaccine Immunology 9, no. 3 (May 2002): 588–97. http://dx.doi.org/10.1128/cdli.9.3.588-597.2002.
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ABSTRACT The reliability of an in vitro pyrogen test system based on proinflammatory cytokine release from human monocytic cells was assessed by comparison with a test system based on a human whole blood culture as well as with the conventional rabbit pyrogen test. The human cells used as the pyrogen indicator cells were newly selected by subcloning of a human monocytic cell line, Mono-Mac-6. The selected cells, named MM6-CA8, responded to various pyrogens, including endotoxin, peptidoglycan (PG), Staphylococcus aureus Cowan 1 (SAC), and poly(I · C), with a high sensitivity and produced proinflammatory cytokines, such as interleukin 1 (IL-1), IL-6, and tumor necrosis factor alpha. Among these cytokines, IL-6 was produced most sensitively in response to traces of the pyrogens and detected in the largest quantities in the culture medium. The cytokine-producing responses of MM6-CA8 cells correlated significantly with the responses of cultured human whole blood, which represents an ex vivo culture test system reproducing pyrogen-induced cytokine production in the human body. In terms of cytokine inducibility, the pyrogens were ranked in the order endotoxin > PG > poly (I · C) > SAC in both culture systems, a ranking which almost agreed with the ranking of their pyrogenicity as assessed by the rabbit pyrogen test. These results suggest that the in vitro responsiveness of MM6-CA8 cells to various pyrogens is highly relevant for human pyrogenic reactions. Therefore, the in vitro test system is useful and reliable for detecting the presence of materials that are pyrogenic for humans.
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Carson, Danielle, Sophie Myhill, Elena Palmieri, Francesca Necchi, Sjoerd Rijpkema, Francesca Micoli, Ida Karin Nordgren, Omar Rossi, and Caroline Vipond. "Development of a Monocyte Activation Test as an Alternative to the Rabbit Pyrogen Test for Mono- and Multi-Component Shigella GMMA-Based Vaccines." Microorganisms 9, no. 7 (June 24, 2021): 1375. http://dx.doi.org/10.3390/microorganisms9071375.
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Generalised modules for membrane antigens (GMMA)-based vaccines comprise the outer membrane from genetically modified Gram-negative bacteria containing membrane proteins, phospholipids and lipopolysaccharides. Some lipoproteins and lipopolysaccharides are pyrogens; thus, GMMA-based vaccines are intrinsically pyrogenic. It is important to control the pyrogenic content of biological medicines, including vaccines, to prevent adverse reactions such as febrile responses. The rabbit pyrogen test (RPT) and bacterial endotoxin test (BET) are the most commonly employed safety assays used to detect pyrogens. However, both tests are tailored for detecting pyrogenic contaminants and have considerable limitations when measuring the pyrogen content of inherently pyrogenic products. We report the adaptation of the monocyte activation test (MAT) as an alternative to the RPT for monitoring the pyrogenicity of Shigella GMMA-based vaccines. The European Pharmacopoeia endorses three MAT methods (A–C). Of these, method C, the reference lot comparison test, was identified as the most suitable. This method was evaluated with different reference materials to ensure parallelism and consistency for a mono- and multi-component Shigella GMMA vaccine. We demonstrate the drug substance as a promising reference material for safety testing of the matched drug product. Our results support the implementation of MAT as an alternative to the RPT and use of the defined parameters can be extended to GMMA-based vaccines currently in development, aiding vaccine batch release.
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Wang, Mingren, Shanshan Dong, Hong Shao, Can Wang, and Gang Chen. "The Optimization of HL60-IL6 Assay and its Application in the Pyrogen Detection of Monoclonal Antibody." Current Pharmaceutical Analysis 16, no. 3 (March 31, 2020): 319–27. http://dx.doi.org/10.2174/1573412914666180627142302.
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Background: The HL60-IL6 assay has been initially established, but the process of the assay and calculation was not simplified. And there are no reports on whether it can be applied to detect pyrogen contamination in the monoclonal antibody. Objective: The study aimed to improve the HL60/IL-6 assay and detect the pyrogens in the monoclonal antibody drug by HL60-IL6 assay. Methods: The human promyelocytic leukemia cell line (HL-60) was incubated with pyrogen standard solution, such as lipopolysaccharide (LPS), zymosan and lipoteichoic acid (LTA),or monoclonal antibody sample solution for 48 hours, and then cytokines interleukin-6 (IL-6),secreted from HL-60, were measured by ELISA. The study further described the standard curves on OD (Optical Density) value of IL-6 responding to pyrogen stimulation, and determined the content of pyrogen in the monoclonal antibody production after validation. In addition, the sensitivity of HL60 to three pyrogens was evaluated to establish one standard curve to determine endotoxin and non-endotoxin level. Then, the credibility of standard curves was evaluated. After improvement of the assay, 9 monoclonal antibody batches were assayed for pyrogens in parallel with the Rabbit Pyrogen Test (RPT) and HL60/IL-6 assay. Results: It was achieved that the standard curve between OD value of IL-6 and pyrogen concentration was established. Then, it was found that the sensitivity of HL60 responding to LPS was the weakest, as a result of which, only LPS standard curve needs to be described in each test for detection of pyrogens. Besides, to evaluate the credibility of standard curve, the parameters of the standard curve were restricted and the resulting interpretation was also specified. 3 Bevacizumab batches failed the RPT, which also showed pyrogenic contamination by the HL60/IL-6 assay. Conclusion: HL60-IL6 assay was improved and can be applied to pyrogen detection of monoclonal antibody.
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Bibaeva, A. Yu. "Decode space images to monitoring of geosystem pyrogenic transformation." Geodesy and Cartography 930, no. 12 (January 20, 2018): 31–38. http://dx.doi.org/10.22389/0016-7126-2017-930-12-31-38.
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The paper describes the methodology for processing remote sensing data to indicate pyrogenic effects on natural geosystems. Autumn season space images (from the end of the firedangerous period to the beginning of the formation of the snow cover – the end of September to the beginning of October) with a less than 20 % cloud level were preferred. The area affected by fires within Priolhonye in the period since 2013 to 2015 years are analyzed. According to the obtained data it has made more than 200 km2. Pyrogene impact on Priolkhonye geosystems considerably amplifies amidst transforming environmental factors (climate warming, decrease in water level of the Lake Baikal and all that) and anthropogenic impacts, that is lead to change in the structure and rate of physiographic processes. In the conditions of the changing environment of geodynamic active area this impact on Priolhonye geosystems can be disastrous and lead to their irreversible transformation. In particular, disturbed geosystems of cedar forests by fire will could change to pine-larch forests through the birch series. In particular, the destructive effect of the pyrogenic factor on steep slopes with pine-larch rarefied groups of facies leads to the destruction of its invariant structure and replacement by steppe small-graingrassy lithophilic ones.
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Wibaut, J. P., and Elisabeth Dingemanse. "Über eine Pyrogene Umlagerung von n-Methyl-(α-Pyridyl)-α-Pyrrol." Recueil des Travaux Chimiques des Pays-Bas 45, no. 9 (September 3, 2010): 671–73. http://dx.doi.org/10.1002/recl.19260450908.
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Redford, Jane, Isis Bishai, and Flavio Coceani. "Pyrogen–prostaglandin coupling in the pathogenesis of fever: evidence against a role for nitric oxide." Canadian Journal of Physiology and Pharmacology 73, no. 10 (October 1, 1995): 1466–74. http://dx.doi.org/10.1139/y95-204.
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There is much debate on the mechanism by which blood-borne pyrogens trigger prostaglandin E2 (PGE2) synthesis in brain and fever. This investigation was undertaken to determine whether nitric oxide qualifies as a signal transducer for pyrogens at the interface between blood and brain. Experiments were carried out in vitro and in vivo using, respectively, preparations of cerebral tissue and microvessels from the rat, and the conscious, chronically instrumented cat. In vitro preparations produced PGE2 and its production increased during a 30-min treatment with interleukin 1 (brain tissue) or endotoxin (microvessels). In addition, both pyrogens increased cyclic GMP levels in cerebral microvessels. In both brain tissue and microvessels, NG-nitro-L-arginine had no effect on basal PGE2 release, while it curtailed the pyrogen-stimulated release. The same treatment reduced the cyclic GMP accumulation brought about by pyrogens in the microvessels. Conversely, in the conscious cat, inhibitors of nitric oxide synthesis (NG-monomethyl-L-argimne, NG-nitro-L-arginine) had no effect on fever and the concomitant elevation of PGE2 in cerebrospinal fluid, regardless of the pyrogen used (endotoxin, interleukin 1) and the route of administration (intravenous, intracerebroventricular). We conclude that nitric oxide may serve as a pyrogen mediator in brain. This mediator function, however, is seemingly not important in the development of fever.Key words: pyrogen, fever mechanism, nitric oxide, prostaglandin E2, blood–brain barrier.
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Bibby, D. C., and R. F. Grimble. "Effect of age on hypothalamic prostaglandin E2 production and fever in response to tumour necrosis factor (cachectin) and endotoxin in rats." Clinical Science 81, no. 3 (September 1, 1991): 313–17. http://dx.doi.org/10.1042/cs0810313.
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1. Decreased febrile responses to interleukin-1 and endotoxin have been noted in a number of species with ageing. 2. The present study extends these observations by examining the pyrogenic response to intravenous recombinant human tumour necrosis factor-α (50 μg/kg) using conscious rats aged 7,20 and 80 weeks. 3. The febrile response decreased in magnitude and duration with age. Fevers of 0.9 °C and of 5 h duration were observed in the youngest rats, whereas those aged 80 weeks were afebrile. The depression in serum zinc level and the elevation in liver zinc level, which occurred 7 h after injection, were unaffected by age. 4. The mechanism of the reduced pyrogenic response was examined by assessing prostaglandin E2 production in vitro from hypothalami of rats, aged 10 and 24 weeks, in response to Escherichia coli endotoxin and tumour necrosis factor. 5. Whereas the production of prostaglandin E2 increased by 47% and 52%, respectively, in hypothalami from 10-week-old rats, no response to either pyrogen was obtained in tissue from rats aged 24 weeks. 6. Maturity brings about a decreased responsiveness of hypothalamic prostaglandin E2 production to pyrogens, which may explain the decreased febrile responses observed.
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de Mattos, Katherine Antunes, Elaine Cristina Azevedo Navega, Vitor Fernandes Silva, Alessandra Santos Almeida, Cristiane Caldeira da Silva, Octavio Augusto França Presgrave, Daniel da Silva Guedes Junior, and Isabella Fernandes Delgado. "Applicability of the Monocyte Activation Test (MAT) in the Quality Control of the 17DD Yellow Fever Vaccine." Alternatives to Laboratory Animals 46, no. 1 (March 2018): 23–37. http://dx.doi.org/10.1177/026119291804600107.
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The need for alternatives to animal use in pyrogen testing has been driven by the Three Rs concept. This has resulted in the inclusion of the monocyte activation test (MAT) in the European Pharmacopoeia, 2010. However, some technical and regulatory obstacles must be overcome to ensure the effective implementation of the MAT by the industry, especially for the testing of biological products. The yellow fever (YF) vaccine (17DD-YFV) was chosen for evaluation in this study, in view of: a) the 2016–2018 outbreak of YF in Brazil; b) the increase in demand for 17DD-YFV doses; c) the complex production process with live attenuated virus; d) the presence of possible test interference factors, such as residual process components (e.g. ovalbumin); and e) the need for the investigation of other pyrogens that are not detectable by the methods prescribed in the YF vaccine monograph. The product-specific testing was carried out by using cryopreserved and fresh whole blood, and IL-6 and IL-1β levels were used as the marker readouts. After assessing the applicability of the MAT on a 1:10 dilution of 17DD-YFV, endotoxin and non-endotoxin pyrogens were quantified in spiked batches, by using the lipopolysaccharide and lipoteichoic acid standards, respectively. The quantitative analysis demonstrated the correlation between the MAT and the Limulus amoebocyte lysate (LAL) assays, with respect to the limits of endotoxin recovery in spiked batches and the detection of no pyrogenic contamination in commercial batches of 17DD-YFV. The data demonstrated the applicability of the MAT for 17DD-YFV pyrogen testing, and as an alternative method that can contribute to biological quality control studies.
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Korpa, A., R. Trettin, K. G. Böger, J. Thieme, and C. Schmidt. "Pozzolanic reactivity of nanoscale pyrogene oxides and their strength contribution in cement-based systems." Advances in Cement Research 20, no. 1 (January 2008): 35–46. http://dx.doi.org/10.1680/adcr.2008.20.1.35.
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du Plessis, I., D. Mitchell, H. P. Laburn, and T. Cartmell. "Fever and lethargy induced by subcutaneous pyrogen infusion in unrestrained rats." Canadian Journal of Physiology and Pharmacology 83, no. 11 (November 1, 2005): 1007–14. http://dx.doi.org/10.1139/y05-065.
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We have investigated the effects of continuous subcutaneous infusion of lipopolysaccharide (LPS), muramyldipeptide (MDP), or saline on abdominal temperature and voluntary activity in unrestrained rats. Both pyrogens were infused via osmotic pumps at a rate of ~2 µg·kg–1·min–1 for 7 d. LPS infusion evoked a 3-d and MDP a 1-d elevation in body temperature. Night-time activity was suppressed on days 1 and 2 during LPS infusion and on day 1 of MDP infusion. Body mass was significantly decreased on infusion day 4 in rats receiving either LPS or MDP; however, the rate of weight gain had been restored by day 8 (1 d after cessation of pyrogen infusion). We further tested the body temperature response of the same experimental animals to a single subcutaneous bolus injection (250 µg/kg) of the same pyrogen that had been infused for 7 d, 2 d after cessation of pyrogen infusion (day 9). The fever response in rats receiving a bolus injection of either LPS or MDP was significantly attenuated in rats that had previously been infused with the same pyrogen. These data suggest that tolerance developed to continuous infusion of both Gram-negative and Gram-positive pyrogens, and that mechanisms of tolerance development set in early during the 7-d infusion period of both pyrogens and persisted for at least 2 d after the cessation of pyrogen infusion. We propose that cytokine intermediates were involved or required in inducing these responses to continuous infusion of both LPS and MDP.Key words: lipopolysaccharide, muramyldipeptide, rats, osmotic pump, tolerance, Gram-negative, Gram-positive, sickness behavior.
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Tindall, Brendan, Dogan Demircioglu, and Thomas Uhlig. "Recombinant bacterial endotoxin testing: a proven solution." BioTechniques 70, no. 5 (May 2021): 290–300. http://dx.doi.org/10.2144/btn-2020-0165.
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Testing of parenteral pharmaceuticals and medical devices for pyrogens (fever-inducing substances) is critical to patient safety. The original rabbit pyrogen test has largely been replaced by different bacterial endotoxin tests based on Limulus amebocyte lysate (LAL), sourced from the blood equivalent of horseshoe crabs after comparative studies to the rabbit pyrogen test. Since 2004 a bacterial endotoxin test based on recombinant factor C (rFC), the endotoxin sensor protein inside of LAL, has been used as an animal-free alternative to LAL. Likewise, numerous studies compared LAL and rFC. Here we describe the history of pyrogen and bacterial endotoxin testing and summarize the evidence presented by those studies. We demonstrate that rFC and LAL are equivalent and comparable.
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Franco, Elvira, Verónica Garcia-Recio, Pilar Jiménez, Manuel Garrosa, Tomás Girbés, Manuel Cordoba-Diaz, and Damián Cordoba-Diaz. "Endotoxins from a Pharmacopoeial Point of View." Toxins 10, no. 8 (August 16, 2018): 331. http://dx.doi.org/10.3390/toxins10080331.
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A pyrogen is a substance that causes fever after intravenous administration or inhalation. Gram negative endotoxins are the most important pyrogens to pharmaceutical laboratories. In the International, United States, Japanese and European Pharmacopoeias, there are two official methods to evaluate pyrogenicitythat is, the bacterial endotoxin test, and the pyrogen test. The main objective of this review is to compare the monographs of each test among the different Pharmacopeias, to detect similarities and differences. The former can be considered fully harmonized, and only non-significant differences were detected. The latter, which is the only available assay for some products and formulations to demonstrate apyrogenicity, shows large differences, which should be considered.
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Kato, Nobuo. "Pyrogenicity of human adenoviruses." Journal of General Virology 81, no. 11 (November 1, 2000): 2611–16. http://dx.doi.org/10.1099/0022-1317-81-11-2611.
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High doses (>1·56×107 p.f.u.) of purified preparations of human adenovirus types 3, 5 and 8 exhibited definite pyrogenic activity when injected intravenously into rabbits. Complete pyrogenic tolerance was obtained not only with homologous types but also with heterologous types of adenovirus. No pyrogenic cross-tolerance was observed between each of these three adenovirus types and paramyxovirus pyrogen or bacterial lipopolysaccharide. Adenovirus pyrogenicity was retained after UV-inactivation, whereas it was inactivated by heating at 56 °C for 30 min. Adenovirus pyrogenicity was not neutralized by mixing with homologous type-specific antiserum but non-pyrogenic doses (107 p.f.u.) of adenovirus types 3, 5 and 8 became highly pyrogenic in the presence of type-specific antibodies at the optimal virus:antibody ratio. This enhanced pyrogenicity depended upon the virus–antibody complex. From these results, it is probable that the pyrogenic activity of the virus–antibody complex, rather than the pyrogenic activity of the virions, is the main contributor to fever in adenovirus infection under actual physiological conditions.
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Borisiuk, M. V., and V. V. Zinchuk. "Analysis of the relationship between hemoglobin-oxygen affinity and lipid peroxidation during fever." Acta Biochimica Polonica 42, no. 1 (March 31, 1995): 69–74. http://dx.doi.org/10.18388/abp.1995_4670.
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Endogenous hyperthermia was induced in rabbits by i.v. pyrogenal administration. Hemoglobin-oxygen affinity and parameters of free radical lipid oxidation in plasma and red blood cells were measured. The content of diene conjugates, malonic dialdehyde and Schiff bases were determined at a pyrogenal dose of 4 minimal pyrogenic doses/kg, and iron-initiated chemiluminescence, catalase activity and alpha-tocopherol concentration were determined at 6 minimal pyrogenic doses/kg. A rightward shift of the real oxyhemoglobin dissociation curve and activation of lipid peroxidation were observed. Relationships between the parameters measured were analyzed. Decreased hemoglobin-oxygen affinity is considered to be a possible mechanism of activation of free radicals during fever.
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Zurovsky, Y., Helen Laburn, D. Mitchell, and A. P. MacPhail. "Responses of baboons to traditionally pyrogenic agents." Canadian Journal of Physiology and Pharmacology 65, no. 6 (June 1, 1987): 1402–7. http://dx.doi.org/10.1139/y87-220.
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It is not clear whether baboons develop fever in response to endotoxin or other pyrogens. We injected various pyrogens intravenously in 12 unrestrained baboons (Papio ursinus) and measured their body temperature using intra-abdominal radio-telemeters. Serum iron concentration was also measured. The baboons developed fever after injection of killed Staphylococcus aureus (5 × 107 organisms/kg). No significant fever was measured after injection of lipopolysaccharide (Salmonella typhosa) (0.1, 8, 40, and 100 μg/kg), bovine serum albumin (4 mg/kg), killed Salmonella minnesota (5 × 107 organisms/kg), and killed Salmonella typhi (5 × 107 organisms/kg). A significant decrease in serum iron concentration was found only after injection of S. aureus and lipopolysaccharide, 100 μg/kg. The phagocytic synthesis of interleukin-1 following pyrogen stimulation in baboons and some other primates appears to differ from that in man and in nonprimates.
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Pittman, Quentin J., and Marshall F. Wilkinson. "Central arginine vasopressin and endogenous antipyresis." Canadian Journal of Physiology and Pharmacology 70, no. 5 (May 1, 1992): 786–90. http://dx.doi.org/10.1139/y92-104.
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Arginine vasopressin (AVP) is a centrally synthesized nonapeptide that exerts classical endocrine effects as well as a host of centrally mediated actions. A strong case can be argued in support of a neurotransmitter–neuromodulator role for AVP. Acting within the central nervous system (CNS), AVP has been demonstrated to be involved in the modulation of febrile body temperature. Because AVP acts to reduce pyrogen-induced fevers, but not normal body temperature, its actions are deemed to be antipyretic. However, to demonstrate an endogenous antipyretic function, AVP must be shown to be active during conditions where fever is naturally suppressed. This review will focus on five such conditions where the absence of pyrogen-induced fever can be linked to the endogenous activity of AVP within the brain. In the neonatal rat pup, the use of specific antagonists to the AVP receptor has revealed a role for CNS AVP in the absence of fever following peripheral injections of bacterial endotoxin. These results may help to explain a similar lack of fever in other newborn species. In parturient animals a reduced or absent febrile response has been linked to the increased presence of AVP within the septal area of the brain. The combined use of AVP receptor antagonism as well as immunohistochemistry has shown enhanced AVP activity within the ventral septal area of the rat and guinea pig brain during tolerance to intravenous pyrogens. These results suggest that the mechanism of fever suppression following repeated systemic injections of bacterial pyrogen includes centrally acting AVP. Recent observations from our laboratory have revealed a suppression of fever during the rising phase of arterial blood pressure in the one-kidney, one-clip model of hypertension. The normal febrile response to prostaglandin E1 can be restored in this instance by blockade of ventral septal AVP receptors. A similar situation of lack of response to pyrogens occurs in hypotensive animals in which pressor mechanisms are activated to restore blood pressure to normal. In this, and the previous four examples, centrally acting AVP has been linked to the natural suppression of pyrogen-induced fevers. Using these models of endogenous antipyresis we will continue to investigate this phenomenon to assess the benefits to the organism as well as to examine other nonthermal host defence responses.Key words: fever, antipyretic, pyrogen, host defence, vasopressin.
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Shido, O., T. Nagasaka, and T. Watanabe. "Blunted febrile response to intravenous endotoxin in starved rats." Journal of Applied Physiology 67, no. 3 (September 1, 1989): 963–69. http://dx.doi.org/10.1152/jappl.1989.67.3.963.
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The effects of fasting on the febrile responses to intravenous injection of bacterial lipopolysaccharide (LPS; endotoxin) of Escherichia coli were investigated in rats. Ad libitum-fed rats (C) produced a biphasic fever with an increase in the temperature difference between brown adipose tissue and colon and shivering activity (SA). Measurement by a direct calorimeter showed no particular changes in heat loss. Rats starved for 4 days (F4) responded to intravenous LPS with a monophasic fever accompanied by an increase in SA only. However the maximal rise in colonic temperature (Tco) did not differ from C rats. Subsequent 2-day fasting reduced SA and the maximal fever height. Endogenous pyrogen (EP) injected intravenously produced a prompt rise in Tco followed by prolonged hyperthermia in C rats. In the F4 rats, there was no such sustained rise in Tco as a result of intravenous EP. The response in Tco to intravenous prostaglandin E2 (PGE2) was the same in fed and starved rats. The administration of LPS, EP, and PGE2 into the lateral ventricle evoked a similar extent of hyperthermia in C and F4 rats. Because the second phase of fever has been shown to occur after pyrogens are translated into a febrile stimulus within the blood-brain barrier, it is assumed that the functional changes of the blood-brain barrier such as in the permeability of pyrogens or in the sensitivity of pyrogen receptors resulted in the absence of the second phase of fever in starved rats.
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Stitt, J. T. "A study of the variability in the febrile responses of rabbits to endogenous pyrogen." Journal of Applied Physiology 59, no. 4 (October 1, 1985): 1254–57. http://dx.doi.org/10.1152/jappl.1985.59.4.1254.
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The range of body temperature increases elicited by a standard dose of endogenous pyrogen (0.5 ml/kg iv) was examined in a population of 26 male New Zealand White rabbits. Although the mean maximum increase in rectal temperature was 0.88 +/- 0.06 degree C (SE), individual responses varied from 0.4 degree to 1.5 degree C. Three representative animals that responded to the standard dose of pyrogen with small, intermediate, and large febrile responses were selected and challenged with the same dose of pyrogen on eight separate occasions, and the variability of these responses was examined. There was little variability within the characteristic responses of any particular animal to the repeated challenges. The variability of the febrile responses elicited by both intravenous and intracerebroventricular administration of the same pyrogen was examined and compared using another group of 11 rabbits. The variability in response to the intravenous route was similar to that found in the larger population, whereas the variation in response to the intracerebroventricular route was smaller, and all 11 animals had fevers that were greater than 1 degrees C. It is concluded that the variability of the febrile responses of rabbits to intravenous pyrogen was due to differences between individual sensitivities of animals to the intravenously administered pyrogen. This difference in sensitivity may be due to a difference in the amount of pyrogen that reaches the putative receptor sites, or to a difference in the density or effectiveness of receptor sites in translating the pyrogenic stimulus into a fever response.
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Luker, Frank I., Duncan Mitchell, and Helen P. Laburn. "Fever and motor activity in rats following day and night injections ofStaphylococcus aureuscell walls." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 279, no. 2 (August 1, 2000): R610—R616. http://dx.doi.org/10.1152/ajpregu.2000.279.2.r610.
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Body temperature and physical activity are affected by both circadian cycles and pyrogens. We injected intraperitoneally 2.5 × 109cell walls of the gram-positive organism Staphylococcus aureus or sterile saline at three different times in the circadian temperature and activity rhythm of Sprague-Dawley rats. Irrespective of whether pyrogen injections were made when the rats were inactive (injection at 0900), just before the nighttime rise in activity and body temperature (1630), or during high activity (2100), the peak body temperature attained and the time to reach peak temperature were indistinguishable. The fever response, as measured by the thermal-response index, was greatest, however, when body temperature and activity were in the lowest phase. Physical activity was inhibited by night but not day injection of S. aureus. Our results provide the first description of experimental fever resulting from a gram-positive pyrogen in rats and the first time an aspect of sickness behavior (suppressed motor activity) has been associated with fever resulting from simulated gram-positive bacterial infection.
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Mattenklott, Markus, and Sandra Boos. "Bewertung amorpher Kieselsäuren an Arbeitsplätzen – Vergleich der Analysenverfahren in Deutschland und den USA/Evaluation of amorphous silicas at workplaces – comparison of the analysis methods in Germany and the USA." Gefahrstoffe 81, no. 03-04 (2021): 109–15. http://dx.doi.org/10.37544/0949-8036-2021-03-04-35.
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Unter dem Begriff amorphe Kieselsäuren wird eine Vielzahl von Stoffen zusammengefasst, die im Wesentlichen aus SiO2 mit unterschiedlichen Anteilen an H2O und in der Regel nur sehr geringen Anteilen anderer Elemente bestehen. Zu diesen gehören z. B. kolloidale Kieselsäuren (pyrogene, Gel- und Fällungskieselsäuren), Kieselglas, Kieselgut, gebrannte und ungebrannte Kieselguren und Kieselrauch. Abhängig von der gesundheitlichen Gefährdung werden Kieselglas, Kieselgut, Kieselrauch und gebrannte Kieselguren mit dem Grenzwert von 0,3 mg/m3 in der alveolengängigen Staubfraktion (A-Staub) und alle übrigen amorphen Kieselsäuren mit dem Grenzwert von 4 mg/m³ in der einatembaren Staubfraktion (E-Staub) bewertet. Neben dem in Deutschland seit Jahrzehnten etablierten Analysenverfahren zur direkten Bestimmung amorpher Kieselsäuren wird in den USA ein indirektes Verfahren eingesetzt, bei dem die amorphe Kieselsäure zunächst durch Glühen in Cristobalit umgewandelt wird (NIOSH Manual of Analytical Methods, NMAM 7501). Aktuelle Versuchsreihen konnten zeigen, dass abhängig von der Art der amorphen Kieselsäuren und deren Glühbedingungen unterschiedliche Anteile von Cristobalit ausgebildet werden. Grundsätzlich sind selbst bei Reinstsubstanzen deutliche Minderbefunde durch das indirekte Verfahren festzustellen. Diese fallen noch signifikanter aus, wenn amorphe Kieselsäuren in Mischstäuben auftreten, was die Regel ist. Die Anwendung des amerikanischen Analysenverfahrens kann daher nicht empfohlen werden. Da die Messungen in den USA zudem mit Bezug auf die Staubfraktion „Total Dust“ durchgeführt werden, besteht auch bezüglich der Probenahme keine Möglichkeit, etwaige Datenkollektive beider Länder zu vergleichen.
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Journal, Baghdad Science. "Purification and characterization of Streptococcus pyogenes superantigen (Spe-C)." Baghdad Science Journal 8, no. 4 (December 4, 2011): 956–61. http://dx.doi.org/10.21123/bsj.8.4.956-961.
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From 144 specimens of tonsillitis which were collected from patient, (children of 3 -12 year olds) there were 70 isolates beta hemolytic and 28 isolates were identified as S. pyogenes. Sensitivity of S. pyogenes isolates to antibiotics was tested, all isolates were sensitive to amoxicillin and cephaloxia while higher resistant were to erythromycin. One isolate whiche was 100 A had a stable characteristics and produce pyrogenic toxin was chosen for study and it was purified and characterized from the cell free supernatant of S. pyrogenes strain.
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Nair, Sreelekshmi R., C. S. Geetha, and P. V. Mohanan. "Analysis of IL-1βRelease from Cryopreserved Pooled Lymphocytes in Response to Lipopolysaccharide and Lipoteichoic Acid." BioMed Research International 2013 (2013): 1–10. http://dx.doi.org/10.1155/2013/689642.
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Pyrogens are heterogeneous group of fever-inducing substances derived from Gram-positive and Gram-negative bacteria, fungi, and viruses. They incite immune response by producing endogenous pyrogens such as prostaglandins and other proinflammatory cytokines like IL-1β, IL-6, and TNF-α. The present study was to analyze the influence of cryopreservation in IL-1βrelease, a marker for inflammatory response from human lymphocytes, in response to exogenous pyrogenic stimulants. Lymphocytes isolated from pooled blood of multiple healthy individuals were cryopreserved in DMSO and glycerol for periods of 7, 14, 30, and 60 days and were challenged with LPS and LTAin vitro. The inflammatory cytokine, IL-1βrelease, was measured by ELISA method. It was observed that the release of IL-1βincreases instantaneously after the initiation of incubation and reaches a maximum at 3 to 5 hours and then gradually decreases and gets stabilized for both pyrogens. Moreover it was also observed that the effect of cryoprotectants, DMSO (10%) and glycerol (10%), showed almost similar results for short-term storage, but DMSO-preserved lymphocytes yielded a better viability for long-term storage. Thus, the isolated cryopreserved lymphocytes system can be a promising approach for the total replacement/alteration to animal experimentation for pyrogenicity evaluation.
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Silva, Vitor Fernandes, Daniel da Silva Guedes Junior, Ivna Alana da Silveira, Alessandra Santos Almeida, Fernando de Paiva Conte, Isabella Fernandes Delgado, Cristiane Caldeira Silva, Octavio Augusto França Presgrave, and Katherine Antunes de Mattos. "A Comparison of Pyrogen Detection Tests in the Quality Control of Meningococcal Conjugate Vaccines: The Applicability of the Monocyte Activation Test." Alternatives to Laboratory Animals 46, no. 5 (November 2018): 255–72. http://dx.doi.org/10.1177/026119291804600506.
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The meningococcal C conjugate vaccine (MenCC) is an interesting model with which to test the efficacy of the Monocyte Activation Test (MAT) as an alternative method of pyrogen testing in the quality control of vaccines. The MenCC that has been produced by Bio-Manguinhos in Brazil is in the final development stage, and, as recommended in the guidelines for MenCC production, its pyrogen content must be determined by using the Limulus Amoebocyte Lysate (LAL) assay and the Rabbit Pyrogen Test (RPT). This represents an ideal opportunity to compare LAL and RPT data with data obtained by using a MAT system with cryopreserved whole blood and IL-6/IL-1β as marker readouts. In order to assess the compatibility of the MAT with MenCC, endotoxin and non-endotoxin pyrogen content was quantified by using MenCC samples spiked with lipopolysaccharide (LPS), lipoteichoic acid or zymosan standards. The presence of the aluminium-based adjuvant interfered with the MAT, increasing the readout of IL-1β in LPS-spiked MenCC batches. This infringed the product-specific validation criteria of the test, and led to IL-6 being chosen as the more suitable marker readout. No pyrogenic contaminants were identified in the MenCC batches tested, demonstrating consistency among the different systems (MAT, RPT and the LAL assay). In conclusion, the introduction of the MAT during MenCC development could contribute to the elimination of animal tests post-licensing, ensuring human protection based on an effective non-animal based method of quality control.
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Derijk, R. H., M. Van Kampen, N. Van Rooijen, and F. Berkenbosch. "Hypothermia to endotoxin involves reduced thermogenesis, macrophage-dependent mechanisms, and prostaglandins." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 266, no. 1 (January 1, 1994): R1—R8. http://dx.doi.org/10.1152/ajpregu.1994.266.1.r1.
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At a subthermoneutral ambient temperature of 24 degrees C, intravenous administration of bacterial endotoxin (lipopolysaccharide, LPS) to rats resulted in hypothermia associated with a fall in oxygen consumption followed by fever. At the thermoneutral ambient temperature of 30 degrees C, animals only responded to LPS with fever. The hypothermia and reduction in oxygen consumption were attenuated in rats with eliminated peripheral macrophages. By contrast, macrophage elimination did not affect the febrile response to LPS. Both the hypothermia and the febrile response to LPS were prevented by peripheral administration of the cyclooxygenase inhibitor indomethacin. We conclude that hypothermia in response to LPS is caused by reduced thermogenesis, involves antipyretic products released from peripheral macrophages, and is mediated by prostaglandins. In addition, the febrile response likewise involves prostaglandins, but in contrast to the hypothermia appears to be independent of pyrogens released from peripheral macrophages. Previously, we reported the induction of the pyrogen interleukin-1 in the brain during the time course of the febrile response to LPS (34). The latter observations support the hypothesis that the second phase of biphasic fever is mediated by synthesis and action of pyrogens inside the blood-brain barrier.
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Moosová, Zdena, Lenka Šindlerová, Barbora Ambrůzová, Gabriela Ambrožová, Ondřej Vašíček, Mirna Velki, Pavel Babica, and Lukáš Kubala. "Lipopolysaccharides from Microcystis Cyanobacteria-Dominated Water Bloom and from Laboratory Cultures Trigger Human Immune Innate Response." Toxins 11, no. 4 (April 11, 2019): 218. http://dx.doi.org/10.3390/toxins11040218.
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Massive toxic blooms of cyanobacteria represent a major threat to water supplies worldwide. Here, the biological activities of lipopolysaccharide (LPS) isolated from Microcystis aeruginosa, the most prominent cyanobacteria in water bloom, were studied. LPS was isolated from complex environmental water bloom samples dominated by M. aeruginosa, and from laboratory cultures of non-axenic as well as axenic M. aeruginosa strains PCC7806 and HAMBI/UHCC130. Employing human blood-based in vitro tests, the LPS isolated from complex water bloom revealed the priming of both major blood phagocyte population monocytes and polymorphonuclear leukocytes documented by the increased surface expression of CD11b and CD66b. This was accompanied by a water bloom LPS-mediated dose-dependent induction of tumor necrosis factor α, interleukin-1β, and interleukin-6 production. In accordance with its priming effects, water bloom LPS induced significant activation of p38 and ERK1/2 kinases, as well as NF-κB phosphorylation, in isolated polymorphonuclear leukocytes. Interestingly, the pro-inflammatory potential of LPS from the axenic strain of M. aeruginosa was not lower compared to that of LPS isolated from non-axenic strains. In contrast to the biological activity, water bloom LPS revealed almost twice higher pyrogenicity levels compared to Escherichia coli LPS, as analyzed by the PyroGene test. Moreover, LPS from the non-axenic culture exhibited higher endotoxin activity in comparison to LPS from axenic strains. Taking the above findings together, M. aeruginosa LPS can contribute to the health risks associated with contamination by complex water bloom mass.
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Englisch, M., A. Lindner, M. Krüger, and G. Stumpf. "Bestimmungen von CRP und Neopterin sowie antiendotoxischer Antikörper bei Pferden mit Fieber." Tierärztliche Praxis Ausgabe G: Großtiere / Nutztiere 36, no. 02 (2008): 110–18. http://dx.doi.org/10.1055/s-0038-1623941.
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Zusammenfassung Gegenstand: Feldstudie zum Fieber unbekannter Genese beim Pferd. Ziel: Die routinemäßigen Laborparameter wurden hinsichtlich ihrer Wertigkeit für eine ätiologische Diagnose analysiert. Das diagnostische Profil wurde durch die Parameter CRP und Neopterin sowie durch antiendotoxische Antikörper erweitert. Grundlage der Studie war die Hypothese, dass Endotoxine mit ihrem fieberauslösenden Potenzial eine ätiologische Bedeutung haben könnten. Material und Methoden: Über einen Zeitraum von drei Jahren wurden 383 Fieberfälle untersucht und entsprechend der klinischen Symptomatik in vier verschiedene Fiebertypen eingeteilt. Die Voraussetzung für die Einordnung in die Gruppe 1 (Fieber unbekannter Genese) war der Ausschluss einer anderen Fieberursache bei der Erst- und den Nachuntersuchungen. Die Blutprobe wurde am ersten Untersuchungstag entnommen. Die Bestimmungen von CRP und Neopterin sowie der antiendotoxischen Antikörper erfolgten jeweils mit einem ELISA. In die Auswertung dieser Messergebnisse wurde deren Korrelation zu weiteren klinisch-chemischen Parametern einbezogen. Ergebnisse: Bei 195 (50,9%) Patienten wurde Fieber unbekannter Genese registriert. Während der mittlere CRP-Wert (8,08 g/l) im Normbereich lag, war die Neopterinkonzentration (7,29 mmol/l) erhöht. Die Mittelwerte für die antiendotoxischen Antikörpertiter der Immunglobulinklasse M waren pathologisch erhöht (Anti-Lipid-A-IgM 1,18 OD, Anti-Endotoxin-IgM 1,5 OD). Klinische Relevanz: Das pyrogene Potenzial der Endotoxine ist bei Fällen von Fieber unbekannter Genese in die ätiologischen Betrachtungen mit einzubeziehen. Nach Ausschluss anderer Fieberursachen ist eine diesbezügliche Erweiterung des labordiagnostischen Profils sinnvoll. Neopterin und CRP stellen unspezifische Effektparameter dar, die im Zusammenhang mit weiteren Befunden auch beim Pferd für die Beurteilung des Gesundheitszustandes wertvoll sein können.
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Johnson Rowsey, Pamela. "Thermoregulation: Cytokines Involved in Fever and Exercise." Annual Review of Nursing Research 31, no. 1 (October 2013): 19–46. http://dx.doi.org/10.1891/0739-6686.31.19.
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The study of fever has provided important models in understanding the cells, chemical messengers, and anatomic structures that are involved in inflammation and thermoregulation as a result of infection, stress, or trauma. After contact with a pathogen or an inflammatory stimulus, cells are activated to produce endogenous pyrogens called cytokines. Cytokine functions include a cascade of nonspecific immune responses by target leukocytes and reticuloendothelial cells inducing the synthesis of acute phase proteins by the liver, direct pyrogenic activities via the supraoptic nuclei and the hypothalamus to increase the thermoregulatory set-point (and, thus, induce fever), and a wide spectrum of additional immune effects.
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Negishi, Chiharu, Rainer Lenhardt, Daniel I. Sessler, Jan De Witte, Takehiko Ikeda, Andrea Kurz, and Errol Lobo. "Desflurane Reduces the Febrile Response to Administration of Interleukin-2." Anesthesiology 88, no. 5 (May 1, 1998): 1162–69. http://dx.doi.org/10.1097/00000542-199805000-00005.
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Background Intraoperative fever is relatively rare considering how often pyrogenic causes are likely to be present and how common fever is postoperatively. This low incidence suggests that general anesthesia per se inhibits the normal response to pyrogenic stimulation. The authors therefore tested the hypothesis that desflurane-induced anesthesia produces a dose-dependent inhibition of the febrile response. Methods Eight volunteers were studied, each on 3 study days. Each was given an intravenous injection of 50,000 IU/ kg of interleukin-2 (elapsed time, 0 h), followed 2 h later by 100,000 IU/kg. One hour after the second dose, the volunteers were assigned randomly to three doses of desflurane to induce anesthesia: (1) 0.0 minimum alveolar concentration (MAC; control), (2) 0.6 MAC, and (3) 1.0 MAC. Anesthesia continued for 5 h. Core temperatures were recorded from the tympanic membrane. Thermoregulatory vasoconstriction was evaluated using forearm-minus-fingertip skin temperature gradients; shivering was evaluated with electromyography. Integrated and peak temperatures during anesthesia were compared with repeated-measures analysis of variance and Scheffé's F tests. Results Values are presented as mean +/- SD. Desflurane reduced the integrated (area under the curve) febrile response to pyrogen, from 7.7 +/- 2.0 degrees C x h on the control day to 2.1 +/- 2.3 degrees C x h during 0.6 MAC and to -1.4 +/- 3.1 degrees C x h during 1.0 MAC desflurane-induced anesthesia. Peak core temperature (elapsed time, 5-8 h) decreased in a dose-dependent fashion: 38.6 +/- 0.5 degrees C on the control day, 37.7 +/- 0.7 degrees C during 0.6 MAC and 37.2 +/- 1.0 degrees C during 1.0 MAC desflurane anesthesia. Rising core temperature was always associated with fingertip vasoconstriction and often with shivering. Conclusions Desflurane-induced anesthesia produced a dose-dependent decrease in integrated and peak core temperatures after administration of pyrogen, with 1.0 MAC essentially obliterating fever. Anesthetic-induced inhibition of the pyrogenic response is therefore one reason that fever is an inconsistent clinical response to inflammation during surgery.
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Peterbauer, Anja, Ernst R. Werner, and Gabriele Werner-Felmayer. "Neopterin and Nitrite in Supernatants from Interferon-γ-treated Monocytoid Cell Lines: A Tool to Identify Bacterial Pyrogens." Pteridines 10, no. 3 (August 1999): 112–18. http://dx.doi.org/10.1515/pteridines.1999.10.3.112.
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Summary The rabbit pyrogen assay identifies pyrogenic contaminations in drugs i.l1tend~d for parenteral use. In order to replace this test because of ethical and economical reasons, various in vitro methods have been developed in recent years. Here, we summarize our results on optimizing a test based on using interferony- treated monocytoid cell lines from man (THP-l) and mouse (RAW264.7). The read-out of the test is neopterin or nitrite, respectively, which is released into the supernatant in response to bacterial compounds. These are costimuli of the enzymes involved in neopterin and nitrite formation, i.e. GTP cyclohydrolase I and inducible nitric oxide synthase. The test reproducibly detects cell wall components from Gram-negative as well as from Gram-positive bacteria and mycobacteria. Furthermore, DNA and cell-free supernatants containing a number of bioactive but not further characterized proteins, both from Staphylococcus aureus, can be detected. Thus, this test is superior over the only in vitro alternative accepted in certain cases, namely the limulus amebocyte lysate assay. Results obtained by measuring neopterin or nitrite correlate well with formation of the endogenous pyrogen tumor necrosis factor-a, a read-out used by some other cell-based in vitro alternatives to the rabbit pyrogen test. We therefore think that the assay presented here has the potential to reduce or even replace the animal test.
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Miert, A. S. J. P. A. M. van, and A. Atmakusuma. "Comparative Observations on the Production of Fever by Bacterial Pyrogens and Leucocytic Pyrogen in Goats and Rabbits." Zentralblatt für Veterinärmedizin Reihe A 17, no. 2 (May 13, 2010): 174–84. http://dx.doi.org/10.1111/j.1439-0442.1970.tb01047.x.
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Milton, N. G. N., E. W. Hillhouse, and A. S. Milton. "Modulation of the prostaglandin responses of conscious rabbits to the pyrogen polyinosinic: polycytidylic acid by corticotrophin-releasing factor-41." Journal of Endocrinology 138, no. 1 (July 1993): 7–11. http://dx.doi.org/10.1677/joe.0.1380007.
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ABSTRACT The pyrogenic interferon inducer polyinosinic: polycytidylic acid (Poly I: C) was shown to stimulate rises in both prostaglandin E2 (PGE2) and prostaglandin F2α (PGF2α) in conscious rabbits in vivo. Poly I:C (2·5 μg/kg) stimulated a fivefold rise in circulating immunoreactive (ir) PGE2, with a lag phase of 60 min, which was sustained during the subsequent 4-h period of observation. Poly I:C also stimulated a 2·5-fold rise in circulating irPGF2α with a lag phase of 90 min, which was followed by a return to basal levels after 5 h. The rises in circulating irPGE2 and irPGF2α stimulated by Poly I:C were prevented by pretreatment with the non-steroidal anti-inflammatory drug ketoprofen. Both the irPGE2 and irPGF2α responses to Poly I:C (2·5 μg/kg, i.v.) were antagonized by the corticotrophin-releasing factor-41 (CRF-41) receptor antagonist (α-helical CRF (9–41), 25 μg/kg, i.v.) administered 5 min prior to the pyrogen. Peripheral immunoneutralization using an anti-CRF-41 monoclonal antibody (KCHMB001, 2·5 mg/kg, i.v.) administered 5 min prior to the pyrogen, also inhibited both the PGE2 and PGF2α responses to Poly I:C (2·5 μg/kg, i.v.). However, control mouse IgG also inhibited the PGE2 response. In conclusion, these results suggest a modulatory role for endogenous peripheral CRF-41 in the circulating prostaglandin responses to the pyrogen Poly I: C and this effect may be responsible for the antipyretic actions of peripherally administered CRF-41 antagonists and antibodies. Journal of Endocrinology (1993) 138, 7–11
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Moesby, Lise, Erik W. Hansen, and Jens D. Christensen. "Ultrasonication of pyrogenic microorganisms improves the detection of pyrogens in the Mono Mac 6 assay." European Journal of Pharmaceutical Sciences 11, no. 1 (July 2000): 51–57. http://dx.doi.org/10.1016/s0928-0987(00)00080-4.
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Dudek, K., and D. Bednarek. "Cellular immune response of pigeons in the conditions of endotoxin fever and pyrogenic tolerance." Polish Journal of Veterinary Sciences 14, no. 1 (December 1, 2011): 127–33. http://dx.doi.org/10.2478/v10181-011-0018-7.
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Cellular immune response of pigeons in the conditions of endotoxin fever and pyrogenic toleranceThe aim of this study was to investigate changes in selected parameters of cellular immune response in the conditions of endotoxin fever and pyrogenic tolerance in pigeons. On the first day of observation the experimental birds (n=18) were intravenously injected withEscherichia coliLPS at a dose of 10 μg/kg b.w., while the control animals (n=6) received apyrogenic physiological saline also in the form of injection. On the second and the third day of the experiment LPS was injected additionally at 24 h intervals. Four and a half hours after the saline and pyrogen administration blood samples were collected from the control and experimental pigeons. The following immunological assays were performed: WBC, leucogram and immunophenotyping of lymphocyte subsets in peripheral blood, i.e. CD 3+(T lymphocytes), CD 4+(T helper lymphocytes) and CD 8+(T suppressor/ cytotoxic lymphocytes) cells. In the conditions of endotoxin fever (i.e. after the first LPS injection) leucopenia, monocytopenia, heterophilia and eosinophilia were observed. Additionally, the immunophenotyping of peripheral blood lymphocytes indicated an increase in percentage of CD 3+, CD 4+and CD 8+cells in response to the single injection of LPS. In contrast, the consecutive injections of LPS, which created a pyrogenic tolerance effect, caused a decrease in WBC value, heteropenia, eosinopenia and lymphocytosis. Moreover, during this state an increase in percentage of CD 3+and CD 8+cells was demonstrated in contrast to the percentage of CD 4+lymphocytes. The general tendencies in cellular immune response of the affected pigeons in the conditions of endotoxin fever and pyrogenic tolerance aim at activation of defence mechanisms against LPS for its prompt elimination from the animal's organism.
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Miert, A. S. J. P. A. M., and C. Th M. Duin. "The Effects of Bacterial Pyrogens and Leucocytic Pyrogen Upon Gastric Motility and Heart Rate Frequency in Conscious Goats." Zentralblatt für Veterinärmedizin Reihe A 21, no. 8 (May 13, 2010): 692–702. http://dx.doi.org/10.1111/j.1439-0442.1974.tb01353.x.
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Coceani, F., J. Lees, and I. Bishai. "Further evidence implicating prostaglandin E2 in the genesis of pyrogen fever." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 254, no. 3 (March 1, 1988): R463—R469. http://dx.doi.org/10.1152/ajpregu.1988.254.3.r463.
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Conscious cats were used to study the effects of endotoxin and interleukin 1 (IL 1) on levels of prostaglandin (PG) E2 and thromboxane (TX) B2 (the stable TXA2 byproduct) in cerebrospinal fluid (CSF) from the third ventricle. Pyrogens were given intravenously or intraventricularly and prostanoids were measured by radioimmunoassay. PGE2 was normally less abundant than TXB2 (mean, 37 vs. 528 pg/ml), and its level increased severalfold during the sustained fever following intravenous endotoxin (bolus) or IL 1 (bolus plus infusion). PGE2 elevation preceded the fever and was maintained thereafter. Likewise, intraventricular pyrogens promoted PGE2 formation, and their effect was also manifest during the latent period of the fever. The PGE2 metabolite, 13,14-dihydro-15-keto-PGE2, was not measurable in CSF from either afebrile or febrile animals. Basal content of PGE2, on the other hand, was higher in animals pretreated with probenecid (30 mg/kg ip or iv; 50 or 100 micrograms ivt), confirming the importance of transport processes in removing prostanoids from brain. Unlike PGE2, TXB2 levels did not change during the fever to intravenous endotoxin. TXB2 rose instead in response to intraventricular endotoxin, although the elevation did not extend beyond fever uprise. Furthermore, a TXA2 analog (ONO-11113;2 or 4 micrograms ivt) had inconsistent effects on body temperature, while a TXA2 antagonist (ONO-11120;2 micrograms ivt) did not interfere with endotoxin fever. These findings strongly support a causative role for PGE2 in the onset and progression of pyrogen fever. No evidence of a similar role was obtained for TXA2.
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Dinarello, C. A., J. G. Cannon, S. M. Wolff, H. A. Bernheim, B. Beutler, A. Cerami, I. S. Figari, M. A. Palladino, and J. V. O'Connor. "Tumor necrosis factor (cachectin) is an endogenous pyrogen and induces production of interleukin 1." Journal of Experimental Medicine 163, no. 6 (June 1, 1986): 1433–50. http://dx.doi.org/10.1084/jem.163.6.1433.
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Recombinant human tumor necrosis factor (rTNF alpha) injected intravenously into rabbits produces a rapid-onset, monophasic fever indistinguishable from the fever produced by rIL-1. On a weight basis (1 microgram/kg) rTNF alpha and rIL-1 produce the same amount of fever and induce comparable levels of PGE2 in rabbit hypothalamic cells in vitro; like IL-1, TNF fever is blocked by drugs that inhibit cyclooxygenase. At higher doses (10 micrograms/kg) rTNF alpha produces biphasic fevers. The first fever reaches peak elevation 45-55 min after bolus injection and likely represents a direct action on the thermoregulatory center. During the second fever peak (3 h later), a circulating endogenous pyrogen can be shown present using passive transfer of plasma into fresh rabbits. This likely represents the in vivo induction of IL-1. In vitro, rTNF alpha induces the release of IL-1 activity from human mononuclear cells with maximal production observed at 50-100 ng/ml of rTNF alpha. In addition, rTNF alpha and rIFN-gamma have a synergistic effect on IL-1 production. The biological activity of rTNF alpha could be distinguished from IL-1 in three ways: the monophasic pyrogenic activity of rIL-1 was destroyed at 70 degrees C, whereas rTNF alpha remained active; anti-IL-1 neutralized IL-1 but did recognize rTNF alpha or natural cachectin nor neutralize its cytotoxic effect; and unlike IL-1, rTNF alpha was not active in the mitogen-stimulated T cell proliferation assay. The possibility that endotoxin was responsible for rTNF alpha fever and/or the induction of IL-1 was ruled-out in several studies: rTNF alpha produced fever in the endotoxin-resistant C3H/HeJ mice; the IL-1-inducing property of rTNF alpha was destroyed either by heat (70 degrees C) or trypsinization, and was unaffected by polymyxin B; pyrogenic tolerance to daily injections of rTNF alpha did not occur; levels of endotoxin, as determined in the Limulus amebocyte lysate, were below the minimum rabbit pyrogen dose; and these levels of endotoxin were confirmed by gas chromatography/mass spectrometry analysis for the presence of beta-hydroxymyristic acid. Although rTNF alpha is not active in T cell proliferation assays, it may mimic IL-1 in a T cell assay, since high concentrations of rTNF alpha induced IL-1 from epithelial or macrophagic cells in the thymocyte preparations. These studies show that TNF (cachectin) is another endogenous pyrogen which, like IL-1 and IFN-alpha, directly stimulate hypothalamic PGE2 synthesis. In addition, rTNF alpha is an endogenous inducer of IL-1.(ABSTRACT TRUNCATED AT 400 WORDS)
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Derijk, R. H., P. J. Strijbos, N. van Rooijen, N. J. Rothwell, and F. Berkenbosch. "Fever and thermogenesis in response to bacterial endotoxin involve macrophage-dependent mechanisms in rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 265, no. 5 (November 1, 1993): R1179—R1183. http://dx.doi.org/10.1152/ajpregu.1993.265.5.r1179.
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Increases in thermogenesis and body temperature (fever) frequently accompany infection or injury and are thought to be mediated by endogenous pyrogens (e.g. cytokines), which are released from activated immune cells such as macrophages. Therefore, we have investigated the effect of selective elimination of peripheral macrophages on the changes in oxygen consumption (VO2) and colonic temperature in response to bacterial lipopolysaccharide (LPS) in the rat. Peripheral macrophages were depleted by intravenous injection of liposomes containing the drug dichloromethylene diphosphonate (Cl2MDP). Resting oxygen consumption and colonic temperatures were not affected by macrophage elimination. In intact rats, peripheral injection of LPS (0.1-0.5 mg/kg) elicited an increase in colonic temperature and in oxygen consumption that declined at higher doses (2.5 mg/kg). The pyrogenic and thermogenic responses to LPS were significantly attenuated in rats in which peripheral macrophages were eliminated. Previously, we have reported that elimination of macrophages blunts the plasma interleukin-1 (IL-1) response to LPS. Here we show that elimination of macrophages does not affect the increase in plasma IL-6 concentrations in response to LPS. These data indicate that the pyrogenic and thermogenic responses to LPS are at least in part dependent on mechanisms involving peripheral macrophages, and that peripherally produced IL-1 rather than IL-6 may be an important mediator of the changes in oxygen consumption and colonic temperature in response to LPS.
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Chiba, Seiichi, Emi Itateyama, Kyoko Oka, Takayuki Masaki, Toshiie Sakata, and Hironobu Yoshimatsu. "Hypothalamic Neuronal Histamine Modulates Febrile Response but Not Anorexia Induced by Lipopolysaccharide." Experimental Biology and Medicine 230, no. 5 (May 2005): 334–42. http://dx.doi.org/10.1177/153537020523000507.
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This study examined the contribution of hypothalamic neuronal histamine (HA) to the anorectic and febrlle responses induced by lipopolysaccharide (LPS), an exogenous pyrogen, and the endogenous pyrogens interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α). Intraperitoneal (ip) Injection of LPS, IL-1β, or TNF-α suppressed 24-hr cumulative food intake and increased rectal temperature in rats. To analyze the histamlnergic contribution, rats were pre-treated with intracerebroventricular (icv) injection of 2.44 mmol/ kg or ip injection of 244 mmol/kg of α-fluoromethylhistidine (FMH), a suicide inhibitor of histidine decarboxylase (HDC), to deplete Neural HA. The depletion of neural HA augmented the febrile response to ip Injection of LPS and IL-1ß and alleviated the anorectic response to ip injection of IL-1ß. However, the depletion of neural HA did not modify the LPS-lnduced anorectic response or TNF-α-induced febrile and anorectic responses. Consistent with these results, the rate of hypothalamic HA turnover, assessed by the accumulation of tele-methylhistamine (t-MH), was elevated with ip injections of LPS and IL-1ß, but unaffected by TNF-α at equivalent doses. This suggests that (I) LPS and IL-1ß activate hypothalamic neural HA turnover; (II) hypothalamic neural HA suppresses the LPS- and IL-1β-induced febrile responses and accelerates the IL-1ß-induced anorectic response; and (iii) TNF-α modulates the febrile and anorectic responses via a neural HA-independent pathway. Therefore, hypothalamic neural HA is Involved in the IL-1ß-dominant pathway, rather than the TNF-α-dominant pathway, preceding the systemic Inflammatory response induced by exogenous pyrogens, such as LPS. Further research on this is needed.
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Riveau, G., M. Parant, C. Damais, F. Parant, and L. Chedid. "Dissociation between muramyl dipeptide-induced fever and changes in plasma metal levels." American Journal of Physiology-Cell Physiology 250, no. 4 (April 1, 1986): C572—C577. http://dx.doi.org/10.1152/ajpcell.1986.250.4.c572.
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A fall in plasma iron level and an increase in copper level were observed in rabbits subsequent with the febrile response induced by an intravenous administration of muramyl dipeptide, AcMur-L-Ala-D-isoGln (MDP). The pyrogenic activity of MDP was due partly to the induction of circulating endogenous pyrogen (EP). EP produced in vitro by activated macrophages also elicited changes in iron and copper levels in rabbits. Nonpyrogenic MDP derivatives murabutide [MDP(Gln)-OnBu] and the stereoisomer of MDP [MDP(D,D)] did not cause any change in blood metal levels. Another adjuvant and nonpyrogenic analogue, murametide [MDP(Gln)-OMe], elicited hypoferremia and hypercupremia. Murametide, which has been previously shown to induce secretion of circulating EP but prevents in vivo fever response, was unable to prevent an EP-induced effect on plasma metal concentrations. Injection of supernatant fluids of macrophages incubated with these different glycopeptides showed that only compounds able to induce EP release were capable of evoking hypoferremia and hypercupremia. The EP-containing fluid was 10-fold more active on change in temperature and in plasma metal levels when it was given intracerebroventricularly compared with intravenously. In contrast, a pyrogenic dose of MDP that can act directly on the central thermoregulatory structures did not modify iron and copper levels when it was injected intracerebroventricularly.
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Gimenes, Izabela, Cristiane Caldeira, Octavio Augusto França Presgrave, Wlamir Correa de Moura, and Maria Helena Simões Villas Boas. "Assessment of pyrogenic response of lipoteichoic acid by the monocyte activation test and the rabbit pyrogen test." Regulatory Toxicology and Pharmacology 73, no. 1 (October 2015): 356–60. http://dx.doi.org/10.1016/j.yrtph.2015.07.025.
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Alexander, Brent N., and James E. Fewell. "Metyrapone restores the febrile response to Escherichia coli LPS in pregnant rats." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 300, no. 6 (June 2011): R1588—R1595. http://dx.doi.org/10.1152/ajpregu.00785.2010.
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Fever, an important component of the host's defense response to immune challenge, is absent or attenuated in rats near the term of pregnancy. The present experiments were carried out to determine the role of endogenous glucocorticoids in mediating the altered core temperature (Tc) response to exogenous pyrogen (i.e., Escherichia coli LPS). For the experiments, metyrapone—a glucocorticoid synthesis inhibitor—was administered to near-term pregnant rats prior to an EC100 dose of E. coli LPS. Administration of LPS following vehicle elicited a significant corticosterone response and resulted in a decrease in Tc (i.e., hypothermia). Prior administration of metyrapone, however, which abolished the corticosterone response and altered the pyrogenic/cryogenic cytokine response to LPS, eliminated hypothermia and restored the febrile response. Our results provide evidence that endogenous glucocorticoids play a role in mediating the altered febrile response to immune stimuli observed in rats near the term of pregnancy.
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Kaymak, C., E. Kadioglu, E. Ozcagli, G. Osmanoglu, S. Izdes, C. Agalar, H. Basar, and S. Sardas. "Oxidative DNA damage and total antioxidant status in rats during experimental gram-negative sepsis." Human & Experimental Toxicology 27, no. 6 (June 2008): 485–91. http://dx.doi.org/10.1177/0960327108088972.
Full textAbstract:
Sepsis and septic shock remains as leading cause of death in adult intensive care units. It is widely accepted that gram-negative bacteria and their endotoxins cause sepsis and septic shock, predominantly. Enhanced generation of reactive oxygen species may be responsible for tissue injury in septic shock and endotoxemia. The aim of this study was to assess oxidative DNA damage and the total antioxidant status (TAS) in peripheral lymphocytes of rats during different intraperitoneal gram-negative sepsis stages. Adult male Sprague-Dawley rats were divided randomly into four groups. Control group was intraperitoneally inoculated with 2 mL of pyrogene-free saline (Group I, n = 6), and the other rats received an intraperitoneal inoculum with 2 mL of saline containing 2 × 108 CFU of Escherichia coli. The animals were killed at time zero (Group I, n = 6), at 6th (Group II, n = 7), 12th (Group III, n = 7), and 24th (Group IV, n = 7) hour after the E. coli inoculation. Oxidative DNA damage in peripheral lymphocytes of rats was evaluated by modified comet assay (single-cell gel electrophoresis). Formamidopyrimidine DNA glycosylase (Fpg) and Endonuclease III (Endo III) were used to detect oxidized purines and pyrimidines, respectively. Total antioxidant quantification was carried out using ABTS+ (2,2′-Azino-di-[3 ethylbenzthiazoline sulphonate]) radical formation kinetics (Randox kit) in serum samples. Significant elevations of basal levels of strand breaks (SB) in Group IV were observed as compared with Group I, II, and III. There was a significant increase in Fpg sites in Group III as compared with Group I and II. However, there was no significant difference in terms of Endo III sites in any of the groups. Although the TAS was decreased with the stages of sepsis, this moderate decrease was significant in only Group IV as compared with Group I. There was no statistically significant correlation between DNA damage and TAS for any of the groups.
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Kapas, L., and J. M. Krueger. "Tumor necrosis factor-beta induces sleep, fever, and anorexia." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 263, no. 3 (September 1, 1992): R703—R707. http://dx.doi.org/10.1152/ajpregu.1992.263.3.r703.
Full textAbstract:
The enhanced sleep, fever, and anorexia experienced during general infections are attributed to the increased production of cytokines. Cytokines such as interleukin-1 and tumor necrosis factor-alpha (TNF-alpha) have characteristic somnogenic, pyrogenic, and anorectic effects. TNF-beta is closely related to TNF-alpha, and they share common receptors. The effects of TNF-beta on sleep-wake activity, brain temperature (Tbr), and food intake were, however, heretofore unknown. We injected 0.5-200 ng TNF-beta into rabbits intracerebroventricularly (icv) in the light period, and the electroencephalogram, movement, and Tbr were recorded for 6 h from rabbits. The highest dose, 200 ng TNF-beta, induced increases in non-rapid-eye-movement sleep and decreases in rapid-eye-movement sleep accompanied with biphasic febrile responses. Icv injection of 100 ng TNF-beta at dark onset suppressed 12-h and 24-h food intake in rats. These data suggest to us that TNF-beta may belong to the group of endogenous pyrogens/sleep factors.
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Won, Shen-Jeu, Wu-Tein Huang, Yih-Shyong Lai, and Mao-Tsun Lin. "Staphylococcal Enterotoxin A Acts through Nitric Oxide Synthase Mechanisms in Human Peripheral Blood Mononuclear Cells To Stimulate Synthesis of Pyrogenic Cytokines." Infection and Immunity 68, no. 4 (April 1, 2000): 2003–8. http://dx.doi.org/10.1128/iai.68.4.2003-2008.2000.
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ABSTRACT The pyrogenic response to supernatant fluids obtained from human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin A (SEA) was characteristic of a response to an endogenous pyrogen in that it was brief and monophasic and was destroyed by heating supernatant fluids at 70°C for 30 min. The febrile responses were in parallel with the levels of interleukin-1 (IL-1), tumor necrosis factor (TNF), interferon-γ (IFN-γ), IL-2, and IL-6 in supernatant fluids obtained from PBMC treated with SEA. Both the pyrogenicity and the levels of IL-1, TNF, IFN-γ, IL-2, and IL-6 in supernatant fluids started to rise at 6 to 18 h and reached their peak levels at 24 to 96 h after SEA incubation. Both the fever and the increased levels of IL-1, TNF, IFN-γ, IL-2, and IL-6 in supernatant fluids obtained from the SEA-stimulated PBMC were decreased by incubating SEA-PBMC with anisomycin (a protein synthesis inhibitor), aminoguanidine (an inhibitor of inducible nitric oxide synthase [NOS]), or dexamethasone (an inhibitor of NOS). The febrile response to supernatant fluids obtained from the SEA-stimulated PBMC was attenuated by adding either anti-IL-1β, anti-TNF-α, or anti-IFN-γ monoclonal antibody (MAb) to supernatant fluids. The antipyretic effects exerted by anti-IL-1β MAb were greater than those exerted by anti-TNF-α or anti-IFN-γ MAb. The data suggest that SEA acts through the NOS mechanisms in PBMC to stimulate synthesis of pyrogenic cytokines (in particular, the IL-1β).
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Morimoto, A., T. Nakamori, T. Watanabe, T. Ono, and N. Murakami. "Pattern differences in experimental fevers induced by endotoxin, endogenous pyrogen, and prostaglandins." American Journal of Physiology-Regulatory, Integrative and Comparative Physiology 254, no. 4 (April 1, 1988): R633—R640. http://dx.doi.org/10.1152/ajpregu.1988.254.4.r633.
Full textAbstract:
To distinguish pattern differences in experimentally induced fevers, we investigated febrile responses induced by intravenous (IV), intracerebroventricular (ICV), and intra-preoptic/anterior hypothalamic (POA) administration of bacterial endotoxin (lipopolysaccharide, LPS), endogenous pyrogen (EP), human recombinant interleukin-1 alpha (IL-1), and prostaglandins E2 and F2 alpha (PGE2 and PGF2 alpha). Intravenous LPS, EP, or IL-1 in high concentrations caused biphasic fever. In low concentrations, they induced only the first phase of fever. Latency to onset and time to first peak of fever induced by IV injection of LPS or EP were almost the same as those after ICV or POA injection of PGE2. Fever induced by ICV or POA administration of LPS, EP, IL-1, or PGF2 alpha had a long latency to onset and a prolonged time course. There were significant differences among the latencies to fever onset exhibited by groups that received ICV or POA injections of LPS, EP, or PGF2 alpha and by groups given IV injections of LPS or EP and ICV or POA injections of PGE2. Present observations indicate different patterns of fever produced by several kinds of pyrogens when given by various routes. These results permit us to consider the possibility that there are several mediators or multiprocesses underlying the pathogenesis of fever.
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Caverzasio, J., R. Rizzoli, J. M. Dayer, and J. P. Bonjour. "Interleukin-1 decreases renal sodium reabsorption: possible mechanism of endotoxin-induced natriuresis." American Journal of Physiology-Renal Physiology 252, no. 5 (May 1, 1987): F943—F946. http://dx.doi.org/10.1152/ajprenal.1987.252.5.f943.
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Administration of pyrogen or endotoxins such as Escherichia coli lipopolysaccharide can elicit a marked increase in urinary sodium excretion. This response occurs without any elevation in the filtered load of sodium and it does not appear to be prostaglandin mediated. The various effects produced by endotoxins appear to have interleukin-1 as a common mediator. In the present work, we have studied whether human recombinant interleukin-1 beta (hrIL-1) could affect the renal handling of sodium and thus, could be implicated in natriuretic response to pyrogens or endotoxins. We observed that hrIL-1 intravenously injected into conscious rats provokes a marked increase in sodium excretion. This natriuretic response was not associated with any increase in glomerular filtration rate (clearance of [3H]inulin), nor was it accompanied by significant changes in the urinary excretion of potassium, calcium, or inorganic phosphate. The only concomitant alteration was a decrease in urinary pH. Pretreatment with indomethacin abolished the effect of hrIL-1 on urinary pH but did not modify the natriuretic response. In conclusion, hrIL-1 elicits a selective decrease in tubular sodium reabsorption, which does not appear to involve a change in prostaglandin synthesis. This observation strongly suggests that interleukin-1 could be a key mediator in endotoxin-induced natriuresis.
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ZEISBERGER, EUGEN, and JOACHIM ROTH. "Tolerance to Pyrogens." Annals of the New York Academy of Sciences 856, no. 1 MOLECULAR MEC (September 1998): 116–31. http://dx.doi.org/10.1111/j.1749-6632.1998.tb08320.x.
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Kapiotis, S., J. Besemer, D. Bevec, P. Valent, P. Bettelheim, K. Lechner, and W. Speiser. "Interleukin-4 counteracts pyrogen-induced downregulation of thrombomodulin in cultured human vascular endothelial cells." Blood 78, no. 2 (July 15, 1991): 410–15. http://dx.doi.org/10.1182/blood.v78.2.410.410.
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Abstract Inflammatory mediators such as tumor necrosis factor (TNF) or interleukin-1 (IL-1) and bacterial lipopolysaccharides (LPS) were shown to shift the hemostatic balance of the endothelial cell (EC) surface in favor of procoagulant activities by inducing tissue factor (TF) expression and downregulation of thrombomodulin (TM). In the present study, the effects of IL-4 on these regulatory mechanisms were investigated using cultured human umbilical vein EC. TM downregulation induced by the pyrogens IL-1 (100 U/mL), TNF (500 U/mL), and LPS (20 micrograms/mL) to less than 50% of TM activity of untreated cells during a 12-hour incubation period was completely neutralized when these mediators were coincubated with IL-4 (100 U/mL). In accordance with TM surface activity, TM messenger RNA was decreased by IL-1, TNF, and LPS to less than 40% of untreated cells; this effect was in part antagonized by IL-4. No influence of IL-4 on EC tissue factor induction by IL-1, TNF, and LPS was found. Binding studies using 125I- radiolabeled IL-4 suggest that EC express a single class of high- affinity binding sites (kd = 3.2 pmol/L; 2,000 to 2,500 receptors per cell). These results show that IL-4, in part, protects the EC surface against pyrogen-induced procoagulant changes. Transcriptional regulatory mechanisms seem to be involved in EC surface TM regulation.
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Kapiotis, S., J. Besemer, D. Bevec, P. Valent, P. Bettelheim, K. Lechner, and W. Speiser. "Interleukin-4 counteracts pyrogen-induced downregulation of thrombomodulin in cultured human vascular endothelial cells." Blood 78, no. 2 (July 15, 1991): 410–15. http://dx.doi.org/10.1182/blood.v78.2.410.bloodjournal782410.
Full textAbstract:
Inflammatory mediators such as tumor necrosis factor (TNF) or interleukin-1 (IL-1) and bacterial lipopolysaccharides (LPS) were shown to shift the hemostatic balance of the endothelial cell (EC) surface in favor of procoagulant activities by inducing tissue factor (TF) expression and downregulation of thrombomodulin (TM). In the present study, the effects of IL-4 on these regulatory mechanisms were investigated using cultured human umbilical vein EC. TM downregulation induced by the pyrogens IL-1 (100 U/mL), TNF (500 U/mL), and LPS (20 micrograms/mL) to less than 50% of TM activity of untreated cells during a 12-hour incubation period was completely neutralized when these mediators were coincubated with IL-4 (100 U/mL). In accordance with TM surface activity, TM messenger RNA was decreased by IL-1, TNF, and LPS to less than 40% of untreated cells; this effect was in part antagonized by IL-4. No influence of IL-4 on EC tissue factor induction by IL-1, TNF, and LPS was found. Binding studies using 125I- radiolabeled IL-4 suggest that EC express a single class of high- affinity binding sites (kd = 3.2 pmol/L; 2,000 to 2,500 receptors per cell). These results show that IL-4, in part, protects the EC surface against pyrogen-induced procoagulant changes. Transcriptional regulatory mechanisms seem to be involved in EC surface TM regulation.
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Cai, Tong, Yuan Zhang, Qing He, Qian Liu, Yusheng Pei, Chen Chen, and Hua Gao. "The Suitability of Pyrogen Test in vitro with Human Peripheral Blood Mononuclear Cell for Haemorrhagic Fever with Renal Syndrome Bivalent Vaccine." Journal of Applied Virology 6, no. 3 (October 12, 2017): 19. http://dx.doi.org/10.21092/jav.v6i3.92.
Full textAbstract:
<p>To investigate the suitability of Pyrogen Test in vitro with Human Peripheral Blood Mononuclear Cell (PBMC) for Haemorrhagic Fever with Renal Syndrome Bivalent Vaccine, We collected 9 batches vaccines from different manufacturers. The recovery was determinated by human PBMC- IL-6 in vitro pyrogen test with spiking bacterial endotoxin. The recoveries of batches were between 50%-200%, as the test solutions at a dilution less than the maximum valid dilution (MVD). The results showed all of the 9 batches vaccines were qualified products in pyrogen test. the human PBMC-IL-6 in vitro pyrogen test is suitable for Haemorrhagic Fever with Renal Syndrome Bivalent Vaccine to control the pyrogen. </p>