IL-12 rescues galactosamine-loaded mice from lethal shock triggered by staphylococcal enterotoxin.

Staphylococcal enterotoxin B (SEB) causes lethal shock in D-galactosamine sensitized mice. The lethal shock triggered by SEB is mediated by T cells. We found that the lethal shock was restricted by MHC class II molecule. In addition, consecutive oral exposures to SEB induced tolerance against the shock in the SEB-sensitive mice. To elucidate the tolerance mechanism, the role of anti-inflammatory cytokines was examined. RT-PCR analysis revealed that CD4+ T cells from the SEB-sensitive mice expressed significant levels of IFN-gamma, IL-2, IL-4 and IL-10 mRNA, while those from the tolerant mice exhibited significant levels of IFN-gamma but not IL-2 or IL-4 mRNA. These results indicate that polarity of T helper (Th) cells from Th0 to Th1 was involved in the tolerance to the SEB-induced lethal shock. Lymphoid tissues of the tolerant mice generated mRNA of IL-12, a cytokine which favors Th1 response. It was also demonstrated that intraperitoneal administration of IL-12 conferred protection against the lethal shock in the sensitive mice.