Skip to main content
PMC home page
The Journal of Experimental Medicine logoLink to The Journal of Experimental Medicine
. 1988 Mar 1;167(3):752–761. doi: 10.1084/jem.167.3.752

Toxic shock syndrome toxin 1 as an inducer of human tumor necrosis factors and gamma interferon

PMCID: PMC2188868  PMID: 3127526

Abstract

We present evidence that toxic shock syndrome toxin 1 (TSST-1) induces the production of high levels of TNF by human blood monocytes. Enriched lymphocyte preparations incubated with the staphylococcal toxin produced significant levels of TNF-like activity that is not neutralized by anti-rHuTNF antibodies and is likely to be lymphotoxin (LT or TNF-beta). We demonstrate also that TSST-1 is a potent inducer of IFN-gamma. When lymphocyte preparations were costimulated with PMA, the TSST-1 effect was strongly potentiated and the levels of cytotoxic factors, IFN-gamma, and IL-2 present in supernatant fluids were comparable to those observed after treatment with PMA and PHA. Thus, TSST-1, which is also known as an inducer of IL-1 and IL-2, stimulates the production of endogenous mediators that could play a role in the physiopathological processes of toxic shock syndrome (TSS). The described results suggest that the discrepancies in the clinical features between TSS and endotoxin shock may be related to qualitative differences in cytokine production.

Full Text

The Full Text of this article is available as a PDF (655.0 KB).

Selected References

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

  1. Bauss F., Dröge W., Männel D. N. Tumor necrosis factor mediates endotoxic effects in mice. Infect Immun. 1987 Jul;55(7):1622–1625. doi: 10.1128/iai.55.7.1622-1625.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beutler B., Cerami A. Cachectin/tumor necrosis factor: an endogenous mediator of shock and inflammation. Immunol Res. 1986;5(4):281–293. doi: 10.1007/BF02935501. [DOI] [PubMed] [Google Scholar]
  3. Beutler B., Greenwald D., Hulmes J. D., Chang M., Pan Y. C., Mathison J., Ulevitch R., Cerami A. Identity of tumour necrosis factor and the macrophage-secreted factor cachectin. Nature. 1985 Aug 8;316(6028):552–554. doi: 10.1038/316552a0. [DOI] [PubMed] [Google Scholar]
  4. Beutler B., Milsark I. W., Cerami A. C. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science. 1985 Aug 30;229(4716):869–871. doi: 10.1126/science.3895437. [DOI] [PubMed] [Google Scholar]
  5. Beutler B., Tkacenko V., Milsark I., Krochin N., Cerami A. Effect of gamma interferon on cachectin expression by mononuclear phagocytes. Reversal of the lpsd (endotoxin resistance) phenotype. J Exp Med. 1986 Nov 1;164(5):1791–1796. doi: 10.1084/jem.164.5.1791. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Blomster-Hautamaa D. A., Kreiswirth B. N., Kornblum J. S., Novick R. P., Schlievert P. M. The nucleotide and partial amino acid sequence of toxic shock syndrome toxin-1. J Biol Chem. 1986 Nov 25;261(33):15783–15786. [PubMed] [Google Scholar]
  7. Calvano S. E., Quimby F. W., Antonacci A. C., Reiser R. F., Bergdoll M. S., Dineen P. Analysis of the mitogenic effects of toxic shock toxin on human peripheral blood mononuclear cells in vitro. Clin Immunol Immunopathol. 1984 Oct;33(1):99–110. doi: 10.1016/0090-1229(84)90296-4. [DOI] [PubMed] [Google Scholar]
  8. Cuturi M. C., Murphy M., Costa-Giomi M. P., Weinmann R., Perussia B., Trinchieri G. Independent regulation of tumor necrosis factor and lymphotoxin production by human peripheral blood lymphocytes. J Exp Med. 1987 Jun 1;165(6):1581–1594. doi: 10.1084/jem.165.6.1581. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gery I., Gershon R. K., Waksman B. H. Potentiation of the T-lymphocyte response to mitogens. I. The responding cell. J Exp Med. 1972 Jul 1;136(1):128–142. doi: 10.1084/jem.136.1.128. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gillis S., Ferm M. M., Ou W., Smith K. A. T cell growth factor: parameters of production and a quantitative microassay for activity. J Immunol. 1978 Jun;120(6):2027–2032. [PubMed] [Google Scholar]
  11. Ikejima T., Dinarello C. A., Gill D. M., Wolff S. M. Induction of human interleukin-1 by a product of Staphylococcus aureus associated with toxic shock syndrome. J Clin Invest. 1984 May;73(5):1312–1320. doi: 10.1172/JCI111334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Izumi S., Hirai O., Hayashi K., Konishi Y., Okuhara M., Kohsaka M., Aoki H., Yamamura Y. Induction of a tumor necrosis factor-like activity by Nocardia rubra cell wall skeleton. Cancer Res. 1987 Apr 1;47(7):1785–1792. [PubMed] [Google Scholar]
  13. Kildahl-Andersen O., Nissen-Meyer J. Production and characterization of cytostatic protein factors released from human monocytes during exposure to lipopolysaccharide and muramyl dipeptide. Cell Immunol. 1985 Jul;93(2):375–386. doi: 10.1016/0008-8749(85)90142-x. [DOI] [PubMed] [Google Scholar]
  14. Kobayashi M., Plunkett J. M., Masunaka I. K., Yamamoto R. S., Granger G. A. The human LT system. XII. Purification and functional studies of LT and "TNF-like" LT forms from a continuous human T cell line. J Immunol. 1986 Sep 15;137(6):1885–1892. [PubMed] [Google Scholar]
  15. Lehmann V., Freudenberg M. A., Galanos C. Lethal toxicity of lipopolysaccharide and tumor necrosis factor in normal and D-galactosamine-treated mice. J Exp Med. 1987 Mar 1;165(3):657–663. doi: 10.1084/jem.165.3.657. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mosmann T. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays. J Immunol Methods. 1983 Dec 16;65(1-2):55–63. doi: 10.1016/0022-1759(83)90303-4. [DOI] [PubMed] [Google Scholar]
  17. Nedwin G. E., Svedersky L. P., Bringman T. S., Palladino M. A., Jr, Goeddel D. V. Effect of interleukin 2, interferon-gamma, and mitogens on the production of tumor necrosis factors alpha and beta. J Immunol. 1985 Oct;135(4):2492–2497. [PubMed] [Google Scholar]
  18. Parsonnet J., Hickman R. K., Eardley D. D., Pier G. B. Induction of human interleukin-1 by toxic-shock-syndrome toxin-1. J Infect Dis. 1985 Mar;151(3):514–522. doi: 10.1093/infdis/151.3.514. [DOI] [PubMed] [Google Scholar]
  19. Poindexter N. J., Schlievert P. M. Toxic-shock-syndrome toxin 1-induced proliferation of lymphocytes: comparison of the mitogenic response of human, murine, and rabbit lymphocytes. J Infect Dis. 1985 Jan;151(1):65–72. doi: 10.1093/infdis/151.1.65. [DOI] [PubMed] [Google Scholar]
  20. Quimby F., Nguyen H. T. Animal studies of toxic shock syndrome. Crit Rev Microbiol. 1985;12(1):1–44. doi: 10.3109/10408418509104424. [DOI] [PubMed] [Google Scholar]
  21. Reeves M. W., Arko R. J., Chandler F. W., Bridges N. B. Affinity purification of staphylococcal toxic shock syndrome toxin 1 and its pathologic effects in rabbits. Infect Immun. 1986 Feb;51(2):431–439. doi: 10.1128/iai.51.2.431-439.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. 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]
  23. Stone R. L., Schlievert P. M. Evidence for the involvement of endotoxin in toxic shock syndrome. J Infect Dis. 1987 Apr;155(4):682–689. doi: 10.1093/infdis/155.4.682. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Tracey K. J., Beutler B., Lowry S. F., Merryweather J., Wolpe S., Milsark I. W., Hariri R. J., Fahey T. J., 3rd, Zentella A., Albert J. D. Shock and tissue injury induced by recombinant human cachectin. Science. 1986 Oct 24;234(4775):470–474. doi: 10.1126/science.3764421. [DOI] [PubMed] [Google Scholar]
  26. Uchiyama T., Kamagata Y., Yan X. J., Kohno M., Yoshioka M., Fujikawa H., Igarashi H., Okubo M., Awano F., Saito-Taki T. Study of the biological activities of toxic shock syndrome toxin-1: II. Induction of the proliferative response and the interleukin 2 production by T cells from human peripheral blood mononuclear cells stimulated with the toxin. Clin Exp Immunol. 1987 Jun;68(3):638–647. [PMC free article] [PubMed] [Google Scholar]
  27. Ulich T. R., del Castillo J., Keys M., Granger G. A. Recombinant human alpha lymphotoxin (tumor necrosis factor-beta) induces peripheral neutrophilia and lymphopenia in the rat. Am J Pathol. 1987 Jul;128(1):5–12. [PMC free article] [PubMed] [Google Scholar]
  28. Wager G. P. Toxic shock syndrome: a review. Am J Obstet Gynecol. 1983 May 1;146(1):93–102. doi: 10.1016/0002-9378(83)90933-x. [DOI] [PubMed] [Google Scholar]
  29. Yamamoto A., Nagamuta M., Usami H., Sugawara Y., Watanabe N., Niitsu Y., Urushizaki I. Release of tumor necrosis factor (TNF) into mouse peritoneal fluids by OK-432, a streptococcal preparation. Immunopharmacology. 1986 Apr;11(2):79–86. doi: 10.1016/0162-3109(86)90027-5. [DOI] [PubMed] [Google Scholar]
  30. de Azavedo J. C., Arbuthnott J. P. Toxicity of staphylococcal toxic shock syndrome toxin 1 in rabbits. Infect Immun. 1984 Nov;46(2):314–317. doi: 10.1128/iai.46.2.314-317.1984. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. de Azavedo J. C., Lucken R. N., Arbuthnott J. P. Effect of toxic shock syndrome toxin 1 on chicken embryos. Infect Immun. 1985 Mar;47(3):710–712. doi: 10.1128/iai.47.3.710-712.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES