Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1958 Feb 28;107(3):415–435. doi: 10.1084/jem.107.3.415

STUDIES ON THE PATHOGENESIS OF FEVER WITH INFLUENZAL VIRUSES

III. THE RELATION OF TOLERANCE TO THE PRODUCTION OF ENDOGENOUS PYROGEN

Elisha Atkins 1, Wei Cheng Huang 1
PMCID: PMC2136682  PMID: 13513910

Abstract

Tolerance to the pyrogenic action of intravenously injected virus has been studied in rabbits given either PR8 strain of influenza A virus or Newcastle disease virus (NDV). The following findings suggest that the capacity of the animal to release an endogenous pyrogen is a critical factor. (a) Viruses produce fever by the release of endogenous pyrogen. (b) Tolerance to the pyrogenic effect of reinjected virus is associated with a decrease or absence of endogenous pyrogen production. (c) Tolerance to virus fever may be induced by the prior injection of endogenous pyrogen. (d) Cross-tolerance has been demonstrated between virus and bacterial endotoxin (typhoid vaccine), both of which cause the release of endogenous pyrogen. A difference has been noted in the mechanism of tolerance to successive injections of virus and of bacterial endotoxin. Repeated injections of endotoxins bring about an accelerated clearance of these substances from the blood stream with the result that there is a diminished stimulus to endogenous pyrogen production. Tolerance to virus, on the other hand, is unaccompanied by changes in the rate at which virus disappears from the circulation. It is postulated that circulating endogenous pyrogen, induced by the injection of a number of pyrogenic agents including viruses, temporarily suppresses the further release of endogenous pyrogen and thereby contributes to virus tolerance.

Full Text

The Full Text of this article is available as a PDF (1.0 MB).

Selected References

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

  1. ATKINS E., ALLISON F., Jr, SMITH M. R., WOOD W. B., Jr Studies on the antipyretic action of cortisone in pyrogen-induced fever. J Exp Med. 1955 Apr 1;101(4):353–366. doi: 10.1084/jem.101.4.353. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. ATKINS E., HUANG W. C. Studies on the pathogenesis of fever with influenzal viruses. I. The appearance of an endogenous pyrogen in the blood following intravenous injection of virus. J Exp Med. 1958 Mar 1;107(3):383–401. doi: 10.1084/jem.107.3.383. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. ATKINS E., HUANG W. C. Studies on the pathogenesis of fever with influenzal viruses. II. The effects of endogenous pyrogen in normal and virus-tolerant recipients. J Exp Med. 1958 Mar 1;107(3):403–414. doi: 10.1084/jem.107.3.403. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. ATKINS E., WOOD W. B., Jr Studies on the pathogenesis of fever. I. The presence of transferable pyrogen in the blood stream following the injection of typhoid vaccine. J Exp Med. 1955 May 1;101(5):519–528. doi: 10.1084/jem.101.5.519. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. ATKINS E., WOOD W. B., Jr Studies on the pathogenesis of fever. II. Identification of an endogenous pyrogen in the blood stream following the injection of typhoid vaccine. J Exp Med. 1955 Nov 1;102(5):499–516. doi: 10.1084/jem.102.5.499. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. BENACERRAF B., SEBESTYEN M. M. Effect of bacterial endotoxins on the reticuloendothelial system. Fed Proc. 1957 Sep;16(3):860–867. [PubMed] [Google Scholar]
  7. BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. II. Characterization of fever-producing substances from polymorphonuclear leukocytes and from the fluid of sterile exudates. J Exp Med. 1953 Nov;98(5):493–508. doi: 10.1084/jem.98.5.493. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. BENNETT I. L., Jr, WAGNER R. R., LeQUIRE V. S. The production of fever by influenzal viruses; tolerance in rabbits to the pyrogenic effect of influenzal viruses. J Exp Med. 1949 Oct;90(4):335–347. doi: 10.1084/jem.90.4.335. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. BIOZZI G., BENACERRAF B., HALPERN B. N. The effect of Salm. typhi and its endotoxin on the phagocytic activity of the reticuloendothelial system in mice. Br J Exp Pathol. 1955 Jun;36(3):226–235. [PMC free article] [PubMed] [Google Scholar]
  10. Beeson P. B., Technical Assistance of Elizabeth Roberts TOLERANCE TO BACTERIAL PYROGENS : I. FACTORS INFLUENCING ITS DEVELOPMENT. J Exp Med. 1947 Jun 30;86(1):29–38. doi: 10.1084/jem.86.1.29. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Beeson P. B., Technical Assistance of Elizabeth Roberts TOLERANCE TO BACTERIAL PYROGENS : II. ROLE OF THE RETICULO-ENDOTHELIAL SYSTEM. J Exp Med. 1947 Jun 30;86(1):39–44. doi: 10.1084/jem.86.1.39. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. DOUGHERTY R. M., GROUPE V. Studies on nonspecific acquired resistance to viral toxicity in mice. Proc Soc Exp Biol Med. 1957 Jul;95(3):593–596. doi: 10.3181/00379727-95-23303. [DOI] [PubMed] [Google Scholar]
  13. FARR R. S., CLARK S. L., Jr, PROFFITT J. E., CAMPBELL D. H. Some humoral aspects of the development of tolerance to bacterial pyrogens in rabbits. Am J Physiol. 1954 May;177(2):269–278. doi: 10.1152/ajplegacy.1954.177.2.269. [DOI] [PubMed] [Google Scholar]
  14. FARR R. S., LeQUIRE V. S. Leukocytic and pyrogenic effects of typhoid vaccine and augmentation by homologous plasma. Proc Soc Exp Biol Med. 1950 Dec;75(3):661–666. doi: 10.3181/00379727-75-18298. [DOI] [PubMed] [Google Scholar]
  15. FRENCH E. L. The pyrogenic effect of the influenza-mumps group of viruses in the laboratory rabbit. Aust J Exp Biol Med Sci. 1952 Dec;30(6):479–488. doi: 10.1038/icb.1952.47. [DOI] [PubMed] [Google Scholar]
  16. GOOD R. A., VARCO R. L. A clinical and experimental study of agammaglobulinemia. J Lancet. 1955 Jun;75(6):245–271. [PubMed] [Google Scholar]
  17. GRANT R. Refractorines to pyrogens, effects of incubation of pyrogen with plasma from normal and refractory donors on the responses of refractory recipients. Am J Physiol. 1953 May;173(2):246–252. doi: 10.1152/ajplegacy.1953.173.2.246. [DOI] [PubMed] [Google Scholar]
  18. LeQUIRE V. S. The augmentation of the thermogenic effects of pyrogens by homologous plasma in rabbits. J Infect Dis. 1951 Mar-Apr;88(2):194–206. doi: 10.1093/infdis/88.2.194. [DOI] [PubMed] [Google Scholar]
  19. PETERSDORF R. G., BENNETT I. L., Jr Studies on the pathogenesis of fever. VII. Comparative observations on the production of fever by inflammatory exudates in rabbits and dogs. Bull Johns Hopkins Hosp. 1957 Jun;100(6):277–286. [PubMed] [Google Scholar]
  20. PETERSDORF R. G., BENNETT I. L., Jr Studies on the pathogenesis of fever. VIII. Fever-producing substances in the serum of dogs. J Exp Med. 1957 Aug 1;106(2):293–314. doi: 10.1084/jem.106.2.293. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. PETERSDORF R. G., KEENE W. R., BENNETT I. L., Jr Studies on the pathogenesis of fever. IX. Characteristics of endogenous serum pyrogen and mechanisms governing its release. J Exp Med. 1957 Dec 1;106(6):787–809. doi: 10.1084/jem.106.6.787. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. ROWLEY D., HOWARD J. G., JENKIN C. R. The fate of 32P-labelled bacterial lipopolysaccharide in laboratory animals. Lancet. 1956 Apr 7;270(6919):366–367. doi: 10.1016/s0140-6736(56)90110-6. [DOI] [PubMed] [Google Scholar]
  23. SMITH R. T., BRAUDE A. I., CAREY F. J. The distribution of Cr51 labeled E. coli endotoxin in the generalized Shwartzman reaction. J Clin Invest. 1957 May;36(5):695–699. doi: 10.1172/JCI103471. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. WAGNER R. R., BENNETT I. L., Jr, LeQUIRE V. S. The production of fever by influenzal viruses; factors influencing the febrile response to single injections of virus. J Exp Med. 1949 Oct;90(4):321–334. doi: 10.1084/jem.90.4.321. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. WAGNER R. R., BENNETT I. L., Jr The production of fever by influenzal viruses; effect of receptor-destroying substances. J Exp Med. 1950 Feb;91(2):135–145. doi: 10.1084/jem.91.2.135. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. WAGNER R. R. Production of fever by influenzal viruses. IV. Tolerance to mumps and influenza pyrogens. Proc Soc Exp Biol Med. 1953 Jul;83(3):612–615. doi: 10.3181/00379727-83-20435. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Experimental Medicine are provided here courtesy of The Rockefeller University Press

RESOURCES