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.
Department of Oral Microbiology, Osaka University Faculty of Dentistry, Suita-Osaka, Japan.
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Takahashi
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Nakagawa
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Xu
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Hamada
D000818:Animals; D016207:Cytokines / Q000096:biosynthesis / Q000235:genetics; D004195:Disease Models, Animal; D004768:Enterotoxins / Q000037:antagonists & inhibitors* / Q000633:toxicity*; D005688:Galactosamine / Q000008:administration & dosage*; D015870:Gene Expression; D007274:Injections, Intraperitoneal; D018664:Interleukin-12 / Q000494:pharmacology*; D008221:Lymphoid Tissue / Q000276:immunology; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012772:Shock, Septic / Q000139:chemically induced / Q000235:genetics / Q000517:prevention & control; D013045:Species Specificity; D013211:Staphylococcus aureus; D018089:Superantigens / Q000633:toxicity; D013601:T-Lymphocytes / Q000276:immunology
D016207:Cytokines; D004768:Enterotoxins; D012333:RNA, Messenger; D018089:Superantigens; D018664:Interleukin-12; C031818:enterotoxin B, staphylococcal; D005688:Galactosamine