Skip to main content
NCBI home page
Infection and Immunity logoLink to Infection and Immunity
. 1997 Jul;65(7):2656–2662. doi: 10.1128/iai.65.7.2656-2662.1997

Staphylococcal enterotoxin A-induced fever is associated with increased circulating levels of cytokines in rabbits.

W T Huang 1, M T Lin 1, S J Won 1
PMCID: PMC175375  PMID: 9199433

Abstract

Rabbits were injected intravenously with 10 to 100 ng of staphylococcal enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interferon (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, and IL-6 just before the injection of SEA. Both colonic temperatures and circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both the fever and the increased circulating levels of IFN, TNF, and IL-2 produced by SEA were decreased by pretreatment with indomethacin (a cyclo-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a protein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethasone (an effective anti-inflammatory and immunosuppressive agent) (4 mg/kg, intravenously) in rabbits. Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and colonic temperatures were monitored. Compared to rabbits that received the single injection of SEA, rabbits that received four consecutive injections of SEA showed a lesser increase in circulating levels of IFN, TNF, and IL-2 as well as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile response elicited by SEA by indomethacin, anisomycin, or dexamethasone is due to prevention by these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repeated injection of SEA is associated with decreased production of these circulating cytokines.

Full Text

The Full Text of this article is available as a PDF (171.8 KB).

Selected References

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

  1. Akarasereenont P., Mitchell J. A., Appleton I., Thiemermann C., Vane J. R. Involvement of tyrosine kinase in the induction of cyclo-oxygenase and nitric oxide synthase by endotoxin in cultured cells. Br J Pharmacol. 1994 Dec;113(4):1522–1528. doi: 10.1111/j.1476-5381.1994.tb17169.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Amano Y., Lee S. W., Allison A. C. Inhibition by glucocorticoids of the formation of interleukin-1 alpha, interleukin-1 beta, and interleukin-6: mediation by decreased mRNA stability. Mol Pharmacol. 1993 Feb;43(2):176–182. [PubMed] [Google Scholar]
  3. Andersson J., Nagy S., Björk L., Abrams J., Holm S., Andersson U. Bacterial toxin-induced cytokine production studied at the single-cell level. Immunol Rev. 1992 Jun;127:69–96. doi: 10.1111/j.1600-065x.1992.tb01409.x. [DOI] [PubMed] [Google Scholar]
  4. Baker P. E., Gillis S., Smith K. A. Monoclonal cytolytic T-cell lines. J Exp Med. 1979 Jan 1;149(1):273–278. doi: 10.1084/jem.149.1.273. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Björk L., Andersson J., Ceska M., Andersson U. Endotoxin and Staphylococcus aureus enterotoxin A induce different patterns of cytokines. Cytokine. 1992 Nov;4(6):513–519. doi: 10.1016/1043-4666(92)90013-h. [DOI] [PubMed] [Google Scholar]
  6. Cannon J. G., Clark B. D., Wingfield P., Schmeissner U., Losberger C., Dinarello C. A., Shaw A. R. Rabbit IL-1. Cloning, expression, biologic properties, and transcription during endotoxemia. J Immunol. 1989 Apr 1;142(7):2299–2306. [PubMed] [Google Scholar]
  7. Clark W. G., Page J. S. Pyrogenic responses to staphylococcal enterotoxins A and B in cats. J Bacteriol. 1968 Dec;96(6):1940–1946. doi: 10.1128/jb.96.6.1940-1946.1968. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coyne D. W., Nickols M., Bertrand W., Morrison A. R. Regulation of mesangial cell cyclooxygenase synthesis by cytokines and glucocorticoids. Am J Physiol. 1992 Jul;263(1 Pt 2):F97–102. doi: 10.1152/ajprenal.1992.263.1.F97. [DOI] [PubMed] [Google Scholar]
  9. Dinarello C. A., Cannon J. G., Wolff S. M. New concepts on the pathogenesis of fever. Rev Infect Dis. 1988 Jan-Feb;10(1):168–189. doi: 10.1093/clinids/10.1.168. [DOI] [PubMed] [Google Scholar]
  10. Fischer H., Dohlsten M., Andersson U., Hedlund G., Ericsson P., Hansson J., Sjögren H. O. Production of TNF-alpha and TNF-beta by staphylococcal enterotoxin A activated human T cells. J Immunol. 1990 Jun 15;144(12):4663–4669. [PubMed] [Google Scholar]
  11. Fujikawa H., Takayama H., Uchiyama T., Igarashi H. Bindings of toxic shock syndrome toxin-1 and staphylococcal enterotoxins A, B, and C to rabbit spleen cells. Microbiol Immunol. 1989;33(5):381–390. doi: 10.1111/j.1348-0421.1989.tb01986.x. [DOI] [PubMed] [Google Scholar]
  12. Gjörloff A., Fischer H., Hedlund G., Hansson J., Kenney J. S., Allison A. C., Sjögren H. O., Dohlsten M. Induction of interleukin-1 in human monocytes by the superantigen staphylococcal enterotoxin A requires the participation of T cells. Cell Immunol. 1991 Oct 1;137(1):61–71. doi: 10.1016/0008-8749(91)90056-h. [DOI] [PubMed] [Google Scholar]
  13. Hart P. H., Whitty G. A., Burgess D. R., Croatto M., Hamilton J. A. Augmentation of glucocorticoid action on human monocytes by interleukin-4. Lymphokine Res. 1990 Summer;9(2):147–153. [PubMed] [Google Scholar]
  14. Hodoval L. F., Morris E. L., Crawley G. J., Beisel W. R. Pathogenesis of lethal shock after intravenous staphylococcal enterotoxin B in monkeys. Appl Microbiol. 1968 Feb;16(2):187–192. doi: 10.21236/ad0666852. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Kasai K., Hattori Y., Nakanishi N., Manaka K., Banba N., Motohashi S., Shimoda S. Regulation of inducible nitric oxide production by cytokines in human thyrocytes in culture. Endocrinology. 1995 Oct;136(10):4261–4270. doi: 10.1210/endo.136.10.7545102. [DOI] [PubMed] [Google Scholar]
  16. Kawabe Y., Ochi A. Programmed cell death and extrathymic reduction of Vbeta8+ CD4+ T cells in mice tolerant to Staphylococcus aureus enterotoxin B. Nature. 1991 Jan 17;349(6306):245–248. doi: 10.1038/349245a0. [DOI] [PubMed] [Google Scholar]
  17. Kluger M. J. Fever: role of pyrogens and cryogens. Physiol Rev. 1991 Jan;71(1):93–127. doi: 10.1152/physrev.1991.71.1.93. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Kobayashi Y., Yoshikawa T., Watanabe N. Tumor cytostasis mediated by LPS- or PSK-activated human plastic-adherent peripheral blood mononuclear cells. Cell Immunol. 1992 Oct 15;144(2):358–366. doi: 10.1016/0008-8749(92)90251-j. [DOI] [PubMed] [Google Scholar]
  19. Lando P. A., Dohlsten M., Kalland T., Sjögren H. O., Carlsson R. The TcR-CD3 complex is required for activation of human lymphocytes with staphylococcal enterotoxin A. Scand J Immunol. 1990 Feb;31(2):133–138. doi: 10.1111/j.1365-3083.1990.tb02752.x. [DOI] [PubMed] [Google Scholar]
  20. Lin J. H., Lin M. T. Nitric oxide synthase-cyclo-oxygenase pathways in organum vasculosum laminae terminalis: possible role in pyrogenic fever in rabbits. Br J Pharmacol. 1996 May;118(1):179–185. doi: 10.1111/j.1476-5381.1996.tb15383.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Liu C. T., Sanders R. P. Modification of lethality induced by staphylococcal enterotoxin B in Dutch rabbits. Am J Vet Res. 1980 Mar;41(3):399–404. [PubMed] [Google Scholar]
  22. Lowenstein C. J., Alley E. W., Raval P., Snowman A. M., Snyder S. H., Russell S. W., Murphy W. J. Macrophage nitric oxide synthase gene: two upstream regions mediate induction by interferon gamma and lipopolysaccharide. Proc Natl Acad Sci U S A. 1993 Oct 15;90(20):9730–9734. doi: 10.1073/pnas.90.20.9730. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Maier J. A., Hla T., Maciag T. Cyclooxygenase is an immediate-early gene induced by interleukin-1 in human endothelial cells. J Biol Chem. 1990 Jul 5;265(19):10805–10808. [PubMed] [Google Scholar]
  24. Marrack P., Kappler J. The staphylococcal enterotoxins and their relatives. Science. 1990 May 11;248(4956):705–711. doi: 10.1126/science.2185544. [DOI] [PubMed] [Google Scholar]
  25. Mikoyan V. D., Voevodskaya N. V., Kubrina L. N., Malenkova I. V., Vanin A. F. The influence of antioxidants and cycloheximide on the level of nitric oxide in the livers of mice in vivo. Biochim Biophys Acta. 1995 Oct 19;1269(1):19–24. doi: 10.1016/0167-4889(95)00092-7. [DOI] [PubMed] [Google Scholar]
  26. Milton A. S., Wendlandt S. A possible role for prostaglandin E1 as a modulator for temperature regulation in the central nervous system of the cat. J Physiol. 1970 Apr;207(2):76P–77P. [PubMed] [Google Scholar]
  27. Misko T. P., Trotter J. L., Cross A. H. Mediation of inflammation by encephalitogenic cells: interferon gamma induction of nitric oxide synthase and cyclooxygenase 2. J Neuroimmunol. 1995 Sep;61(2):195–204. doi: 10.1016/0165-5728(95)00091-f. [DOI] [PubMed] [Google Scholar]
  28. Mitchell J. A., Akarasereenont P., Thiemermann C., Flower R. J., Vane J. R. Selectivity of nonsteroidal antiinflammatory drugs as inhibitors of constitutive and inducible cyclooxygenase. Proc Natl Acad Sci U S A. 1993 Dec 15;90(24):11693–11697. doi: 10.1073/pnas.90.24.11693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Normann S. J., Jaeger R. F., Johnsey R. T. Pathology of experimental enterotoxemia. The in vivo localization of staphylococcal enterotoxin B. Lab Invest. 1969 Jan;20(1):17–25. [PubMed] [Google Scholar]
  30. Pettit G. W., Elwell M. R., Jahrling P. B. Possible endotoxemia in rabbits after intravenous injection of Staphylococcus aureus enterotoxin B. J Infect Dis. 1977 Apr;135(4):646–648. doi: 10.1093/infdis/135.4.646. [DOI] [PubMed] [Google Scholar]
  31. Rameshwar P., Gascón P. Release of interleukin-1 and interleukin-6 from human monocytes by antithymocyte globulin: requirement for de novo synthesis. Blood. 1992 Nov 15;80(10):2531–2538. [PubMed] [Google Scholar]
  32. Rammensee H. G., Kroschewski R., Frangoulis B. Clonal anergy induced in mature V beta 6+ T lymphocytes on immunizing Mls-1b mice with Mls-1a expressing cells. Nature. 1989 Jun 15;339(6225):541–544. doi: 10.1038/339541a0. [DOI] [PubMed] [Google Scholar]
  33. Rellahan B. L., Jones L. A., Kruisbeek A. M., Fry A. M., Matis L. A. In vivo induction of anergy in peripheral V beta 8+ T cells by staphylococcal enterotoxin B. J Exp Med. 1990 Oct 1;172(4):1091–1100. doi: 10.1084/jem.172.4.1091. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Schlievert P. M., Shands K. N., Dan B. B., Schmid G. P., Nishimura R. D. Identification and characterization of an exotoxin from Staphylococcus aureus associated with toxic-shock syndrome. J Infect Dis. 1981 Apr;143(4):509–516. doi: 10.1093/infdis/143.4.509. [DOI] [PubMed] [Google Scholar]
  35. Shalaby M. R., Waage A., Aarden L., Espevik T. Endotoxin, tumor necrosis factor-alpha and interleukin 1 induce interleukin 6 production in vivo. Clin Immunol Immunopathol. 1989 Dec;53(3):488–498. doi: 10.1016/0090-1229(89)90010-x. [DOI] [PubMed] [Google Scholar]
  36. Standiford T. J., Kunkel S. L., Rolfe M. W., Evanoff H. L., Allen R. M., Strieter R. M. Regulation of human alveolar macrophage- and blood monocyte-derived interleukin-8 by prostaglandin E2 and dexamethasone. Am J Respir Cell Mol Biol. 1992 Jan;6(1):75–81. doi: 10.1165/ajrcmb/6.1.75. [DOI] [PubMed] [Google Scholar]
  37. Stiles B. G., Bavari S., Krakauer T., Ulrich R. G. Toxicity of staphylococcal enterotoxins potentiated by lipopolysaccharide: major histocompatibility complex class II molecule dependency and cytokine release. Infect Immun. 1993 Dec;61(12):5333–5338. doi: 10.1128/iai.61.12.5333-5338.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Sugiyama H. Endotoxin-like responses induced by staphylococcal enterotoxin. J Infect Dis. 1966 Apr;116(2):162–170. doi: 10.1093/infdis/116.2.162. [DOI] [PubMed] [Google Scholar]
  39. Sundstedt A., Dohlsten M., Hedlund G., Höidén I., Björklund M., Kalland T. Superantigens anergize cytokine production but not cytotoxicity in vivo. Immunology. 1994 May;82(1):117–125. [PMC free article] [PubMed] [Google Scholar]
  40. Swierkosz T. A., Mitchell J. A., Warner T. D., Botting R. M., Vane J. R. Co-induction of nitric oxide synthase and cyclo-oxygenase: interactions between nitric oxide and prostanoids. Br J Pharmacol. 1995 Apr;114(7):1335–1342. doi: 10.1111/j.1476-5381.1995.tb13353.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  41. Szabó C., Thiemermann C., Wu C. C., Perretti M., Vane J. R. Attenuation of the induction of nitric oxide synthase by endogenous glucocorticoids accounts for endotoxin tolerance in vivo. Proc Natl Acad Sci U S A. 1994 Jan 4;91(1):271–275. doi: 10.1073/pnas.91.1.271. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Vink A., Coulie P. G., Wauters P., Nordan R. P., Van Snick J. B cell growth and differentiation activity of interleukin-HP1 and related murine plasmacytoma growth factors. Synergy with interleukin 1. Eur J Immunol. 1988 Apr;18(4):607–612. doi: 10.1002/eji.1830180418. [DOI] [PubMed] [Google Scholar]
  43. Webb S., Morris C., Sprent J. Extrathymic tolerance of mature T cells: clonal elimination as a consequence of immunity. Cell. 1990 Dec 21;63(6):1249–1256. doi: 10.1016/0092-8674(90)90420-j. [DOI] [PubMed] [Google Scholar]
  44. Westphal O. Bacterial endotoxins. The second Carl Prausnitz Memorial Lecture. Int Arch Allergy Appl Immunol. 1975;49(1-2):1–43. [PubMed] [Google Scholar]
  45. Won S. J., Lin M. T., Ko Y. H., Chuang J. The fever induced by polyriboinosinic:polyribocytidylic acid is not related to interferon synthesis in the rabbit's hypothalamus. J Interferon Res. 1991 Jun;11(3):165–169. doi: 10.1089/jir.1991.11.165. [DOI] [PubMed] [Google Scholar]

Articles from Infection and Immunity are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES