Skip to main content
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1977 May 1;145(5):1288–1298. doi: 10.1084/jem.145.5.1288

The release of an endogenous pyrogen from guinea pig leukocytes in vitro: a new model for investigating the role of lymphocytes in fevers induced by antigen in hosts with delayed hypersensitivity

PMCID: PMC2180670  PMID: 67176

Abstract

Guinea pig periotoneal exudate (PE) cells incubated overnight in vitro with heat-killed Staphylococci released an endogenous pyrogen (EP) that could be assayed by intravenous injection in rabbits. The febrile responses were linearly related to the dosage of EP over an eightfold range. PE cells derived from guinea pigs with delayed hypersensitivity (DH) to bovine gamma globulin (BGG), also released EP when incubated with antigen in vitro. This reaction was specific and did not occur withe PE cells from normal or complete Freund's adjuvant-sensitized guinea pigs. Studies indicated that monos and/or polymorphonuclear leukocytes rather than lymphocytes were the source of EP. However, when incubated with BGG and sufficient dosages of BGG-sensitized lymphocytes, normal PE cells released EP over a 42 h period. These results suggest that antigen stimulates specifically sensitized lymphocytes to release an agent (perhaps a lymphokine) that activates phagocytic cells to release EP. This model offers unique advantages for investigating in vitro the role of the lymphocyte in antigen-induced fever in DH as well as the relationship of this lymphocyte-induced activity to other known biologic activities mediated by antigen stimulated lymphocytes.

Full Text

The Full Text of this article is available as a PDF (626.3 KB).

Selected References

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

  1. ATKINS E., HEIJN C., Jr STUDIES ON TUBERCULIN FEVER. 3. MECHANISMS INVOLVED IN THE RELEASE OF ENDOGENOUS PYROGEN IN VITRO. J Exp Med. 1965 Aug 1;122:207–235. doi: 10.1084/jem.122.2.207. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Atkins E., Feldman J. D., Francis L., Hursh E. Studies on the mechanism of fever accompanying delayed hypersensitivity. The role of the sensitized lymphocyte. J Exp Med. 1972 May 1;135(5):1113–1132. doi: 10.1084/jem.135.5.1113. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. BERLIN R. D., WOOD W. B., Jr STUDIES ON THE PATHOGENESIS OF FEVER. 13. THE EFFECT OF PHAGOCYTOSIS ON THE RELEASE OF ENDOGENOUS PYROGEN BY POLYMORPHONUCLEAR LEUKOCYTES. J Exp Med. 1964 May 1;119:715–726. doi: 10.1084/jem.119.5.715. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. BODEL P. T., ATKINS E. STUDIES IN STAPHYLOCOCCAL FEVER. IV. HYPERSENSITIVITY TO CULTURE FILTRATES. Yale J Biol Med. 1964 Oct;37:130–144. [PMC free article] [PubMed] [Google Scholar]
  5. Bodel P., Atkins E. Human leukocyte pyrogen producing fever in rabbits. Proc Soc Exp Biol Med. 1966 Mar;121(3):943–946. doi: 10.3181/00379727-121-30931. [DOI] [PubMed] [Google Scholar]
  6. Bornstein D. L., Woods J. W. Species specificity of leukocytic pyrogens. J Exp Med. 1969 Oct 1;130(4):707–721. doi: 10.1084/jem.130.4.707. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. David J. R. Macrophage activation by lymphocyte mediators. Fed Proc. 1975 Jul;34(8):1730–1736. [PubMed] [Google Scholar]
  8. David J. R. Mediators produced by sensitized lymphocytes. Fed Proc. 1971 Nov-Dec;30(6):1730–1735. [PubMed] [Google Scholar]
  9. GREY H. M., BRIGGS W., FARR R. S. The passive transfer of sensitivity to antigen-induced fever. J Clin Invest. 1961 Apr;40:703–706. doi: 10.1172/JCI104303. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Mott P. D., Wolff S. M. The association of fever and antibody response in rabbits immunized with human serum albumin. J Clin Invest. 1966 Mar;45(3):372–379. doi: 10.1172/JCI105352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Root R. K., Nordlund J. J., Wolff S. M. Factors affecting the quantitative production and assay of human leukocytic pyrogen. J Lab Clin Med. 1970 Apr;75(4):679–693. [PubMed] [Google Scholar]
  12. Root R. K., Wolff S. M. Pathogenetic mechanisms in experimental immune fever. J Exp Med. 1968 Aug 1;128(2):309–323. doi: 10.1084/jem.128.2.309. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Rosenstreich D. L., Blake J. T., Rosenthal A. S. The peritoneal exudate lymphocyte. I. Differences in antigen responsiveness between peritoneal exudate and lymph node lymphocytes from immunized guinea pigs. J Exp Med. 1971 Nov 1;134(5):1170–1186. doi: 10.1084/jem.134.5.1170. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. UHR J. W., BRANDRISS M. W. Delayed hypersensitivity. IV. Systemic reactivity of guinea pigs sensitized to protein antigens. J Exp Med. 1958 Dec 1;108(6):905–924. doi: 10.1084/jem.108.6.905. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. UHR J. W., SCHARFF M. Delayed hypersensitivity. V. The effect of x-irradiation on the development of delayed hypersensitivity and antibody formation. J Exp Med. 1960 Jul 1;112:65–76. doi: 10.1084/jem.112.1.65. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Waksman B. H., Namba Y. On soluble mediators of immunologic regulation. Cell Immunol. 1976 Jan;21(1):161–176. doi: 10.1016/0008-8749(76)90337-3. [DOI] [PubMed] [Google Scholar]

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

RESOURCES