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. 1978 Aug;281:467–476. doi: 10.1113/jphysiol.1978.sp012433

Endotoxin fever in the new-born guinea-pig and the modulating effects of indomethacin and p-chlorophenylalanine

M Székely 1
PMCID: PMC1282708  PMID: 151737

Abstract

1. At 30 °C ambient temperature E. coli endotoxin injected into the cerebral ventricles evokes a febrile response in 0-3 day-old guinea-pigs. If the dose is sufficiently high, the fever is biphasic: two rising phases separated by a transient fall.

2. At 20 °C ambient temperature the change in body temperature after the endotoxin is still biphasic, but the transient fall is more pronounced and, finally, hypothermia develops. The relatively large surface area of the new-born cannot explain, by itself, the hypothermia.

3. The phasic changes in body temperature following endotoxin administration are unlikely to be mediated by a single central factor, and a sequence of several factors could be postulated.

4. Indomethacin prevents the first-phase febrile rise in body temperature, and also the consequent fall, but not the second-phase rise.

5. p-Chlorophenylalanine pre-treatment prevents the transient fall only, it slightly increases the first-phase rise and does not influence the second-phase rise.

6. Prostaglandins and/or other derivatives of endogenous arachidonic acid in the brain might be responsible for the first rising phase of the endotoxin fever, and might also initiate a central serotonergic mechanism which, in turn, could lead to the transient falling phase between the two rising phases of fever. The mechanism of the second-phase febrile rise in body temperature awaits some other explanation.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Alexander G. Body temperature control in mammalian young. Br Med Bull. 1975 Jan;31(1):62–68. doi: 10.1093/oxfordjournals.bmb.a071243. [DOI] [PubMed] [Google Scholar]
  2. BENNETT I. L., Jr, CLUFF L. E. Bacterial pyrogens. Pharmacol Rev. 1957 Dec;9(4):427–479. [PubMed] [Google Scholar]
  3. Blatteis C. M. Comparison of endotoxin and leukocytic pyrogen pyrogenicity in newborn guinea pigs. J Appl Physiol Respir Environ Exerc Physiol. 1977 Mar;42(3):355–361. doi: 10.1152/jappl.1977.42.3.355. [DOI] [PubMed] [Google Scholar]
  4. Blatteis C. M. Influence of body weight and temperature on the pyrogenic effect of endotoxin in guinea pigs. Toxicol Appl Pharmacol. 1974 Aug;29(2):249–258. doi: 10.1016/0041-008x(74)90062-3. [DOI] [PubMed] [Google Scholar]
  5. Carruba M. O., Bächtold H. P. Pyrogen fever in rabbits pretreated with p-chlorophenylalanine or 5, 6-dihydroxytryptamine. Experientia. 1976 Jun 15;32(6):729–730. doi: 10.1007/BF01919857. [DOI] [PubMed] [Google Scholar]
  6. Cranston W. I., Duff G. W., Hellon R. F., Mitchell D., Townsend Y. Evidence that brain prostaglandin synthesis is not essential in fever. J Physiol. 1976 Jul;259(1):239–249. doi: 10.1113/jphysiol.1976.sp011464. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. DONHOFFER S., SZEGVARI G., VARGANAGY I., JARAI I., HAUG-LASZLO A. Uber die Dynamik der chemischen Warmeregulation der Ratte. Acta Physiol Acad Sci Hung. 1957;13(1):37–56. [PubMed] [Google Scholar]
  8. Des Prez R. M., Oates J. A. Lack of relationship of febrile response to endotoxin and brain stem 5-hydroxytryptamine. Proc Soc Exp Biol Med. 1968 Mar;127(3):793–794. doi: 10.3181/00379727-127-32803. [DOI] [PubMed] [Google Scholar]
  9. FELDBERG W., MYERS R. D. EFFECTS ON TEMPERATURE OF AMINES INJECTED INTO THE CEREBRAL VENTRICLES. A NEW CONCEPT OF TEMPERATURE REGULATION. J Physiol. 1964 Sep;173:226–231. doi: 10.1113/jphysiol.1964.sp007454. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Feldberg W., Saxena P. N. Fever produced by prostaglandin E1. J Physiol. 1971 Sep;217(3):547–556. doi: 10.1113/jphysiol.1971.sp009585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Feldberg W. The Ferrier Lecture, 1974. Body temperature and fever: changes in our views during the last decade. Proc R Soc Lond B Biol Sci. 1975 Nov 18;191(1103):199–229. doi: 10.1098/rspb.1975.0124. [DOI] [PubMed] [Google Scholar]
  12. Giarman N. J., Tanaka C., Mooney J., Atkins E. Serotonin, norepinephrine, and fever. Adv Pharmacol. 1968;6(Pt A):307–317. doi: 10.1016/s1054-3589(08)61186-2. [DOI] [PubMed] [Google Scholar]
  13. Hellon R. F. Monoamines, pyrogens and cations: their actions on central control of bodytemperature. Pharmacol Rev. 1974 Dec;26(4):289–321. [PubMed] [Google Scholar]
  14. Koe B. K., Weissman A. p-Chlorophenylalanine: a specific depletor of brain serotonin. J Pharmacol Exp Ther. 1966 Dec;154(3):499–516. [PubMed] [Google Scholar]
  15. Laburn H., Mitchell D., Rosendorff C. Effects of prostaglandin antagonism on sodium arachidonate fever in rabbits. J Physiol. 1977 May;267(2):559–570. doi: 10.1113/jphysiol.1977.sp011826. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Milton A. S., Wendlandt S. Effects on body temperature of prostaglandins of the A, E and F series on injection into the third ventricle of unanaesthetized cats and rabbits. J Physiol. 1971 Oct;218(2):325–336. doi: 10.1113/jphysiol.1971.sp009620. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Myers R. D. Hypothalamic mechanism of pyrogen action in the cat and monkey in: pyrogens and fever. Ciba Found Symp. 1971:131–153. [PubMed] [Google Scholar]
  18. Pittman Q. J., Cooper K. E., Veale W. L., Van Petten G. R. Fever in newborn lambs. Can J Physiol Pharmacol. 1973 Nov;51(11):868–872. doi: 10.1139/y73-133. [DOI] [PubMed] [Google Scholar]
  19. van Miert A. S., Frens J. The reaction of different animal species to bacterial pyrogens. Zentralbl Veterinarmed A. 1968;15(6):532–543. doi: 10.1111/j.1439-0442.1968.tb00456.x. [DOI] [PubMed] [Google Scholar]

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