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.
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- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- 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]
- Wolf J. E., Rabinowitz L. G. Streptococcal toxic shock-like syndrome. Arch Dermatol. 1995 Jan;131(1):73–77. [PubMed] [Google Scholar]
- 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]
- 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]
- 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]