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. 1961 Nov 30;114(6):939–959. doi: 10.1084/jem.114.6.939

STUDIES ON TUBERCULIN FEVER

II. OBSERVATIONS ON THE ROLE OF ENDOGENOUS PYROGEN IN TOLERANCE

John M Moses 1, Elisha Atkins 1
PMCID: PMC2180408  PMID: 14476462

Abstract

Certain characteristics of tolerance which develops to the pyrogenic effects of old tuberculin (OT) in BCG-vaccinated rabbits have been described. Rabbits made tolerant by several injections of OT lost their ability to produce detectable amounts of endogenous pyrogen (EP) in response to the specific agent (OT) but mobilized normal amounts of EP when given a small unrelated stimulus. On the other hand, when this stimulus followed shortly after an initial tuberculin fever of sufficient magnitude, release of additional EP was suppressed, presumably due to an inhibitory effect of the EP previously mobilized by tuberculin. Similarly, a single large dose of endotoxin almost completely suppressed the response of sensitized rabbits to OT given several hours later. Since several spaced injections of the same dosage were ineffective, this phenomenon does not appear to be attributable to the known mechanisms by which endotoxins promote non-specific resistance to toxicity and infection. Tolerance to tuberculin could not be definitely shown following an injection of Newcastle disease virus which also produces a circulating EP, and it has been inferred that endotoxin blocks the pyrogenic action of antigen on host tissues directly rather than through mobilizing EP. On the basis of these observations, the relationship of specific to non-specific tolerance to tuberculin fever has been compared in terms of the ability of such tolerant animals to mobilize EP to heterologous stimuli and it is concluded that the two forms of tolerance are different. Furthermore, the fact that a number of unrelated agents produce tolerance non-specifically supports the concept that there may be a common source of EP released by a number of stimuli, including endotoxins and myxoviruses, as well as antigen in specifically sensitized hosts.

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Selected References

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  1. 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]
  2. 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]
  3. ATKINS E., HUANG W. C. Studies on the pathogenesis of fever with influenzal viruses. III. The relation of tolerance to the production of endogenous pyrogen. J Exp Med. 1958 Mar 1;107(3):415–435. doi: 10.1084/jem.107.3.415. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. ATKINS E. Pathogenesis of fever. Physiol Rev. 1960 Jul;40:580–646. doi: 10.1152/physrev.1960.40.3.580. [DOI] [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. 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]
  8. 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]
  9. 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]
  10. 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]
  11. 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]
  12. BOEHME D., DUBOS R. J. The effect of bacterial constituents on the resistance of mice to heterologous infection and on the activity of their reticulo-endothelial system. J Exp Med. 1958 Apr 1;107(4):523–536. doi: 10.1084/jem.107.4.523. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. BOYDEN S. V. The immunological response to antigens of the tubercle bacillus; some experimental aspects. Prog Allergy. 1958;5:149–214. doi: 10.1159/000277644. [DOI] [PubMed] [Google Scholar]
  14. 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]
  15. 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]
  16. COLLINS R. D., WOOD W. B., Jr Studies on the pathogenesis of fever. VI. The interaction of leucocytes and endotoxin in vitro. J Exp Med. 1959 Dec 1;110:1005–1016. doi: 10.1084/jem.110.6.1005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. CRANSTON W. I., GOODALE F., Jr, SNELL E. S., WENDT F. The role of leucocytes in the initial action of bacterial pyrogens in man. Clin Sci. 1956 May;15(2):219–226. [PubMed] [Google Scholar]
  18. FAVOUR C. B. Cell injury in allergic inflammation. Int Arch Allergy Appl Immunol. 1957;10(4):193–224. doi: 10.1159/000228377. [DOI] [PubMed] [Google Scholar]
  19. HALL C. H., Jr, ATKINS E. Studies on tuberculin fever. I. The mechanism of fever in tuberculin hypersensitivity. J Exp Med. 1959 Apr 1;109(4):339–359. doi: 10.1084/jem.109.4.339. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. HOWARD J. G., ROWLEY D., WARDLAW A. C. Investigations on the mechanism of stimulation of non-specific immunity by bacterial lipopolysaccharides. Immunology. 1958 Jul;1(3):181–203. [PMC free article] [PubMed] [Google Scholar]
  21. KING M. K., WOOD W. B., Jr Studies on the pathogenesis of fever. IV. The site of action of leucocytic and circulating endogenous pyrogen. J Exp Med. 1958 Feb 1;107(2):291–303. doi: 10.1084/jem.107.2.291. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. KING M. K., WOOD W. B., Jr Studies on the pathogenesis of fever. V. The relation of circulating endogenous pyrogen to the fever of acute bacterial infections. J Exp Med. 1958 Feb 1;107(2):305–318. doi: 10.1084/jem.107.2.305. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. KIRCHHEIMER W. F., WEISER R. S., VAN LIEW R. Tuberculin reaction; transfer of systemic tuberculin sensitivity with cells of tuberculous guinea pigs. Proc Soc Exp Biol Med. 1949 Jan;70(1):99–102. doi: 10.3181/00379727-70-16837. [DOI] [PubMed] [Google Scholar]
  24. LAWRENCE H. S. The delayed type of allergic inflammatory response. Am J Med. 1956 Mar;20(3):428–447. doi: 10.1016/0002-9343(56)90128-0. [DOI] [PubMed] [Google Scholar]
  25. MEIER R., BEIN H. J., JAQUES R. The action of bacterial polysaccharides on allergic phenomena. Int Arch Allergy Appl Immunol. 1957;11(1-2):101–118. doi: 10.1159/000228406. [DOI] [PubMed] [Google Scholar]
  26. PAPPENHEIMER A. M., Jr Hypersensitivity of the delayed type. Harvey Lect. 1956;(SERIES):100–118. [PubMed] [Google Scholar]
  27. RAFTER G. W., COLLINS R. D., WOOD W. B., Jr Studies on the pathogenesis of fever. VII. Preliminary chemical characterization of leucocytic pyrogen. J Exp Med. 1960 Jun 1;111:831–840. doi: 10.1084/jem.111.6.831. [DOI] [PMC free article] [PubMed] [Google Scholar]

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