Skip to main content
Infection and Immunity logoLink to Infection and Immunity
. 1996 Mar;64(3):714–718. doi: 10.1128/iai.64.3.714-718.1996

Interleukins 6 and 11 protect mice from mortality in a staphylococcal enterotoxin-induced toxic shock model.

B E Barton 1, J Shortall 1, J V Jackson 1
PMCID: PMC173827  PMID: 8641771

Abstract

BALB/By mice given doses of D-galactosamine plus Staphylococcus aureus enterotoxin B die within 48 h of administration. The cause of death is a syndrome much like toxic shock syndrome in humans. We used this model to investigate the role of two cytokines, interleukin 6 and interleukin 11, which share the signal transducing subunit, gp130, of their respective receptors. We observed that pretreatment of mice with antibody to interleukin 6 increased mortality from 55% to nearly 90% (P < 0.001), while pretreatment with either cytokine reduced death. The protection was dose dependent; however, interleukin 6 was about 10-fold more potent that interleukin 11. These data indicate that endogenous interleukin 6 plays a protective role in attenuating acute inflammatory responses; furthermore, interleukin 6 and interleukin 11 can abrogate T-cell activation due to triggering by superantigen. A possible clinical role for these cytokines in the treatment of toxic shock merits further investigation.

Full Text

The Full Text of this article is available as a PDF (243.0 KB).

Selected References

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

  1. Aderka D., Le J. M., Vilcek J. IL-6 inhibits lipopolysaccharide-induced tumor necrosis factor production in cultured human monocytes, U937 cells, and in mice. J Immunol. 1989 Dec 1;143(11):3517–3523. [PubMed] [Google Scholar]
  2. Aderka D., Maor Y., Novick D., Engelmann H., Kahn Y., Levo Y., Wallach D., Revel M. Interleukin-6 inhibits the proliferation of B-chronic lymphocytic leukemia cells that is induced by tumor necrosis factor-alpha or -beta. Blood. 1993 Apr 15;81(8):2076–2084. [PubMed] [Google Scholar]
  3. Barton B. E., Jackson J. V. Protective role of interleukin 6 in the lipopolysaccharide-galactosamine septic shock model. Infect Immun. 1993 Apr;61(4):1496–1499. doi: 10.1128/iai.61.4.1496-1499.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Baumann H., Schendel P. Interleukin-11 regulates the hepatic expression of the same plasma protein genes as interleukin-6. J Biol Chem. 1991 Oct 25;266(30):20424–20427. [PubMed] [Google Scholar]
  5. Bean A. G., Freiberg R. A., Andrade S., Menon S., Zlotnik A. Interleukin 10 protects mice against staphylococcal enterotoxin B-induced lethal shock. Infect Immun. 1993 Nov;61(11):4937–4939. doi: 10.1128/iai.61.11.4937-4939.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. 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]
  7. Choi Y., Lafferty J. A., Clements J. R., Todd J. K., Gelfand E. W., Kappler J., Marrack P., Kotzin B. L. Selective expansion of T cells expressing V beta 2 in toxic shock syndrome. J Exp Med. 1990 Sep 1;172(3):981–984. doi: 10.1084/jem.172.3.981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Coulie P. G., Stevens M., Van Snick J. High- and low-affinity receptors for murine interleukin 6. Distinct distribution on B and T cells. Eur J Immunol. 1989 Nov;19(11):2107–2114. doi: 10.1002/eji.1830191121. [DOI] [PubMed] [Google Scholar]
  9. Dellabona P., Peccoud J., Kappler J., Marrack P., Benoist C., Mathis D. Superantigens interact with MHC class II molecules outside of the antigen groove. Cell. 1990 Sep 21;62(6):1115–1121. doi: 10.1016/0092-8674(90)90388-u. [DOI] [PubMed] [Google Scholar]
  10. Du X. X., Neben T., Goldman S., Williams D. A. Effects of recombinant human interleukin-11 on hematopoietic reconstitution in transplant mice: acceleration of recovery of peripheral blood neutrophils and platelets. Blood. 1993 Jan 1;81(1):27–34. [PubMed] [Google Scholar]
  11. Fast D. J., Schlievert P. M., Nelson R. D. Toxic shock syndrome-associated staphylococcal and streptococcal pyrogenic toxins are potent inducers of tumor necrosis factor production. Infect Immun. 1989 Jan;57(1):291–294. doi: 10.1128/iai.57.1.291-294.1989. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Fiorentino D. F., Bond M. W., Mosmann T. R. Two types of mouse T helper cell. IV. Th2 clones secrete a factor that inhibits cytokine production by Th1 clones. J Exp Med. 1989 Dec 1;170(6):2081–2095. doi: 10.1084/jem.170.6.2081. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Hilton D. J., Hilton A. A., Raicevic A., Rakar S., Harrison-Smith M., Gough N. M., Begley C. G., Metcalf D., Nicola N. A., Willson T. A. Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal transduction. EMBO J. 1994 Oct 17;13(20):4765–4775. doi: 10.1002/j.1460-2075.1994.tb06802.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Howard M., Muchamuel T., Andrade S., Menon S. Interleukin 10 protects mice from lethal endotoxemia. J Exp Med. 1993 Apr 1;177(4):1205–1208. doi: 10.1084/jem.177.4.1205. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Johnson H. M., Russell J. K., Pontzer C. H. Staphylococcal enterotoxin microbial superantigens. FASEB J. 1991 Sep;5(12):2706–2712. doi: 10.1096/fasebj.5.12.1916093. [DOI] [PubMed] [Google Scholar]
  16. Markowitz M. Changing epidemiology of group A streptococcal infections. Pediatr Infect Dis J. 1994 Jun;13(6):557–560. doi: 10.1097/00006454-199406000-00032. [DOI] [PubMed] [Google Scholar]
  17. Markowitz M. Changing epidemiology of group A streptococcal infections. Pediatr Infect Dis J. 1994 Jun;13(6):557–560. doi: 10.1097/00006454-199406000-00032. [DOI] [PubMed] [Google Scholar]
  18. Marrack P., Blackman M., Kushnir E., Kappler J. The toxicity of staphylococcal enterotoxin B in mice is mediated by T cells. J Exp Med. 1990 Feb 1;171(2):455–464. doi: 10.1084/jem.171.2.455. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. 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]
  20. Matthys P., Mitera T., Heremans H., Van Damme J., Billiau A. Anti-gamma interferon and anti-interleukin-6 antibodies affect staphylococcal enterotoxin B-induced weight loss, hypoglycemia, and cytokine release in D-galactosamine-sensitized and unsensitized mice. Infect Immun. 1995 Apr;63(4):1158–1164. doi: 10.1128/iai.63.4.1158-1164.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Miethke T., Duschek K., Wahl C., Heeg K., Wagner H. Pathogenesis of the toxic shock syndrome: T cell mediated lethal shock caused by the superantigen TSST-1. Eur J Immunol. 1993 Jul;23(7):1494–1500. doi: 10.1002/eji.1830230715. [DOI] [PubMed] [Google Scholar]
  22. Miethke T., Gaus H., Wahl C., Heeg K., Wagner H. T-cell-dependent shock induced by a bacterial superantigen. Chem Immunol. 1992;55:172–184. [PubMed] [Google Scholar]
  23. Miethke T., Wahl C., Heeg K., Echtenacher B., Krammer P. H., Wagner H. T cell-mediated lethal shock triggered in mice by the superantigen staphylococcal enterotoxin B: critical role of tumor necrosis factor. J Exp Med. 1992 Jan 1;175(1):91–98. doi: 10.1084/jem.175.1.91. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Mihara M., Ikuta M., Koishihara Y., Ohsugi Y. Interleukin 6 inhibits delayed-type hypersensitivity and the development of adjuvant arthritis. Eur J Immunol. 1991 Oct;21(10):2327–2331. doi: 10.1002/eji.1830211006. [DOI] [PubMed] [Google Scholar]
  25. Miller S. D. Postoperative toxic shock syndrome after lumbar laminectomy in a male patient. Spine (Phila Pa 1976) 1994 May 15;19(10):1182–1185. doi: 10.1097/00007632-199405001-00018. [DOI] [PubMed] [Google Scholar]
  26. Nyirjesy P., Jones R. S., Chatwani A., Zinner E. S., Axelrod P. Streptococcal toxic shock-like syndrome as an unusual complication of laparoscopic tubal ligation. A case report. J Reprod Med. 1994 Aug;39(8):649–651. [PubMed] [Google Scholar]
  27. Peavy D. L., Adler W. H., Smith R. T. The mitogenic effects of endotoxin and staphylococcal enterotoxin B on mouse spleen cells and human peripheral lymphocytes. J Immunol. 1970 Dec;105(6):1453–1458. [PubMed] [Google Scholar]
  28. Rhee C. A., Smith R. J., Jackson I. T. Toxic shock syndrome associated with suction-assisted lipectomy. Aesthetic Plast Surg. 1994 Spring;18(2):161–163. doi: 10.1007/BF00454477. [DOI] [PubMed] [Google Scholar]
  29. Sheehan K. C., Ruddle N. H., Schreiber R. D. Generation and characterization of hamster monoclonal antibodies that neutralize murine tumor necrosis factors. J Immunol. 1989 Jun 1;142(11):3884–3893. [PubMed] [Google Scholar]
  30. Starnes H. F., Jr, Pearce M. K., Tewari A., Yim J. H., Zou J. C., Abrams J. S. Anti-IL-6 monoclonal antibodies protect against lethal Escherichia coli infection and lethal tumor necrosis factor-alpha challenge in mice. J Immunol. 1990 Dec 15;145(12):4185–4191. [PubMed] [Google Scholar]
  31. Todd J., Fishaut M., Kapral F., Welch T. Toxic-shock syndrome associated with phage-group-I Staphylococci. Lancet. 1978 Nov 25;2(8100):1116–1118. doi: 10.1016/s0140-6736(78)92274-2. [DOI] [PubMed] [Google Scholar]
  32. Uchiyama T., Yan X. J., Imanishi K., Yagi J. Bacterial superantigens--mechanism of T cell activation by the superantigens and their role in the pathogenesis of infectious diseases. Microbiol Immunol. 1994;38(4):245–256. doi: 10.1111/j.1348-0421.1994.tb01772.x. [DOI] [PubMed] [Google Scholar]
  33. Wolf J. E., Rabinowitz L. G. Streptococcal toxic shock-like syndrome. Arch Dermatol. 1995 Jan;131(1):73–77. [PubMed] [Google Scholar]
  34. Woloski B. M., Smith E. M., Meyer W. J., 3rd, Fuller G. M., Blalock J. E. Corticotropin-releasing activity of monokines. Science. 1985 Nov 29;230(4729):1035–1037. doi: 10.1126/science.2997929. [DOI] [PubMed] [Google Scholar]
  35. Yin T., Taga T., Tsang M. L., Yasukawa K., Kishimoto T., Yang Y. C. Involvement of IL-6 signal transducer gp130 in IL-11-mediated signal transduction. J Immunol. 1993 Sep 1;151(5):2555–2561. [PubMed] [Google Scholar]
  36. de Waal Malefyt R., Abrams J., Bennett B., Figdor C. G., de Vries J. E. Interleukin 10(IL-10) inhibits cytokine synthesis by human monocytes: an autoregulatory role of IL-10 produced by monocytes. J Exp Med. 1991 Nov 1;174(5):1209–1220. doi: 10.1084/jem.174.5.1209. [DOI] [PMC free article] [PubMed] [Google Scholar]

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

RESOURCES