The crucial role of IL-10 in the suppression of the immunological response in mice exposed to staphylococcal enterotoxin B.
Staphylococcal enterotoxin B (SEB), a bacterial superantigen, activates the immune system resulting in a burst of pro- and anti-inflammatory cytokines. A central anti-inflammatory mediator in this process is IL-10. Using IL-10-deficient C57BL/6 (IL-10 KO) mice, we studied the role of endogenous IL-10 in the regulation of the immune response to SEB. SEB (100 microg) induced the release of IL-10 in control C57BL/6 [IL-10 wild type (WT)] mice, but not in their IL-10 KO counterparts. SEB-evoked plasma levels of TNF-alpha, IL-1beta, IL-2, IL-6, IL-12 and IFN-gamma were significantly higher in the IL-10 KO mice than in the WT animals. The release of macrophage inflammatory proteins-1alpha and -2 was also enhanced in the IL-10 KO mice. Further, upon SEB challenge, mice deficient in IL-10 produced higher levels of nitric oxide than the WT animals. IL-10 deficiency resulted in a marked enhancement of the SEB-induced apoptosis of thymocytes. Finally, IL-10 KO mice were more susceptible to SEB-induced lethal shock than their WT controls. These results show that IL-10 plays an important immunoregulatory role in the response to a superantigenic stimulus, by dampening of the shock-inducing inflammatory response and early activation-induced cell death elicited by SEB.
Haskó
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Division of Critical Care Medicine, Children's Hospital Medical Center, Cincinnati, Ohio 45229-3039, USA.
Virág
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L
Egnaczyk
G
G
Salzman
A L
AL
Szabó
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C
D000818:Animals; D016207:Cytokines / Q000276:immunology; D004768:Enterotoxins / Q000276:immunology*; D007109:Immunity; D007165:Immunosuppression Therapy; D007249:Inflammation / Q000276:immunology; D016753:Interleukin-10 / Q000276:immunology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018089:Superantigens / Q000276:immunology*
D016207:Cytokines; D004768:Enterotoxins; D018089:Superantigens; D016753:Interleukin-10; C031818:enterotoxin B, staphylococcal