SYSTEMIC RELEASE AND PROTECTIVE ROLE OF IL-10 IN STAPHYLOCOCCAL-ENTEROTOXIN B-INDUCED SHOCK IN MICE

Staphylococcal enterotoxin B (SEB) is a bacterial superantigen that in duces the production of several pro-inflammatory cytokines, leading to a self-limited shock. In the present study, we show that SEB also tri ggers the systemic release of IL-10, an anti-inflammatory and immunosu ppressive cytokine. Serum IL-10 was undetectable (<1000 pg/ml) in cont rol BALB/c mice and rose to 8500 +/- 2850 pg/ml (mean +/- SEM) 4 h aft er injection of 100 mu g SEB. Cell depletion experiments and analysis of IL-10 mRNA expression indicated that CD4(+) cells played a major ro le in SEB-induced IL-10 production. Pretreatment of mice with neutrali zing anti-IL-10 mAb before SEB challenge did not modify the release of TNF but led to increased and sustained IL-2 and IFN-gamma serum level s. Furthermore, although no lethality occurred in mice injected with S EB and control mAb, injection of anti-IL-10 mAb before SEB resulted in a 30% lethality (p < 0.05). This lethality was completely prevented b y anti-IFN-gamma mAb injection, indicating that IFN-gamma plays a cruc ial role in the increased toxicity of SEB in anti-IL-10 mAb-injected m ice. We conclude that SEB induces the production of IL-10 by CD4(+) ce lls in vivo and that endogenous IL-10 plays an important immunoregulat ory role in this model by down-regulating IL-2 and IFN-gamma productio n.