Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1955 May 1;101(5):519–528. doi: 10.1084/jem.101.5.519

STUDIES ON THE PATHOGENESIS OF FEVER

I. THE PRESENCE OF TRANSFERABLE PYROGEN IN THE BLOOD STREAM FOLLOWING THE INJECTION OF TYPHOID VACCINE

Elisha Atkins 1, W Barry Wood Jr 1
PMCID: PMC2136461  PMID: 14367676

Abstract

The rate of clearance of intravenously injected typhoid vaccine was studied in unsensitized, sensitized, and pyrogen-tolerant rabbits by means of a passive transfer technique. The blood of unsensitized rabbits which had not been previously exposed to bacterial pyrogen remained pyrogenic for normal recipients throughout a period of 2 hours following the injection. In contrast, rabbits sensitized by having received either one or two injections of the vaccine at least 3 weeks prior to the experiment cleared their blood of the test vaccine within 30 minutes despite the fact that they exhibit the same febrile response as unsensitized rabbits. After 1 hour, however, a transferable pyrogenic substance was again demonstrable in the sera of this group. Reasons are discussed for believing that this newly appearing substance may be of endogenous origin and may be the factor which directly affects the thermoregulatory centers of the brain. Rabbits which are made tolerant by repeated daily injections of vaccine have a characteristically depressed febrile response. Not only were the blood streams of such animals cleared of the injected vaccine within less than 5 minutes, but samples of their sera obtained 1 and 2 hours after the injection also failed to contain demonstrable quantities of the secondary pyrogen observed in sensitized animals. The latter observation is in keeping with the suggestion that the secondary pyrogen may play a critical role in the production of fever.

Full Text

The Full Text of this article is available as a PDF (547.5 KB).

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. BENNETT I. L., Jr A study of the relationship between the fever caused by bacterial pyrogens and the fever accompanying acute infections. J Exp Med. 1948 Sep 1;88(3):267–278. doi: 10.1084/jem.88.3.267. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BENNETT I. L., Jr A study of the relationship between the fevers caused by bacterial pyrogens and by the intravenous injection of the sterile exudates of acute inflammation. J Exp Med. 1948 Sep 1;88(3):279–284. doi: 10.1084/jem.88.3.279. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BENNETT I. L., Jr, BEESON P. B. Studies on the pathogenesis of fever. I. The effect of injection of extracts and suspensions of uninfected rabbit tissues upon the body temperature of normal rabbits. J Exp Med. 1953 Nov;98(5):477–492. doi: 10.1084/jem.98.5.477. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. 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]
  6. BENNETT I. L., Jr, BEESON P. B. The effect of cortisone upon reactions of rabbits to bacterial endotoxins with particular reference to acquired resistance. Bull Johns Hopkins Hosp. 1953 Nov;93(5):290–308. [PubMed] [Google Scholar]
  7. BENNETT I. L., Jr, BEESON P. B. The properties and biologic effects of bacterial pyrogens. Medicine (Baltimore) 1950 Dec;29(4):365–400. doi: 10.1097/00005792-195012000-00003. [DOI] [PubMed] [Google Scholar]
  8. BENNETT I. L., Jr, CLUFF L. E. Influence of nitrogen mustard upon reactions to bacterial endotoxins; Shwartzman phenomenon and fever. Proc Soc Exp Biol Med. 1952 Oct;81(1):304–307. doi: 10.3181/00379727-81-19859. [DOI] [PubMed] [Google Scholar]
  9. BERTHRONG M., CLUFF L. E. Studies of the effect of bacterial endotoxins on rabbit leucocytes. I. Effect of intravenous injection of the substances with and without induction of the local Shwartzman reaction. J Exp Med. 1953 Oct;98(4):331–348. doi: 10.1084/jem.98.4.331. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. CHAMBERS W. W., KOENIG H. Site of action in the central nervous system of a bacterial pyrogen. Am J Physiol. 1949 Nov;159(2):209–216. doi: 10.1152/ajplegacy.1949.159.2.209. [DOI] [PubMed] [Google Scholar]
  11. CLUFF L. E. Studies of the effect bacterial endotoxins on rabbit leucocytes. II. Development of acquired resistance. J Exp Med. 1953 Oct;98(4):349–364. doi: 10.1084/jem.98.4.349. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. ESSEX H. E., GRANA A. Behavior of the leukocytes of the rabbit during periods of transient leukopenia variously induced. Am J Physiol. 1949 Sep;158(3):396–400. doi: 10.1152/ajplegacy.1949.158.3.396. [DOI] [PubMed] [Google Scholar]
  13. 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]
  14. GRANT R. Nature of pyrogen fever; effect of environmental temperature on response to typhoid-paratyphoid vaccine. Am J Physiol. 1949 Dec;159(3):511–524. doi: 10.1152/ajplegacy.1949.159.3.511. [DOI] [PubMed] [Google Scholar]
  15. GRANT R., WHALEN W. J. Latency of pyrogen fever; appearance of a fast-acting pyrogen in the blood of febrile animals and in plasma incubated with bacterial pyrogen. Am J Physiol. 1953 Apr;173(1):47–54. doi: 10.1152/ajplegacy.1953.173.1.47. [DOI] [PubMed] [Google Scholar]
  16. LEUSEN I. R., ESSEX H. E. Leukopenia and changes in differential leucocyte counts produced in rabbits by dextran and acacia. Am J Physiol. 1953 Jan;172(1):231–236. doi: 10.1152/ajplegacy.1952.172.1.231. [DOI] [PubMed] [Google Scholar]
  17. 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]
  18. THE PATHOGENESIS of fever. Am J Med. 1955 Mar;18(3):351–353. doi: 10.1016/0002-9343(55)90216-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES