par Florquin, Sandrine ;Amraoui, Z;Dubois, C;Decuyper, Jean ;Goldman, Michel
Référence The Journal of experimental medicine, 180, 3, page (1153-1158)
Publication Publié, 1994
Article révisé par les pairs
Résumé : Nitric oxide (NO) synthesis during experimental endotoxemia has been shown to have both deleterious and beneficial effects. In the present study, we analyzed the in vivo production and the regulatory role of NO in the shock syndrome induced by staphylococcal enterotoxin B (SEB) in mice. First, we found that intraperitoneal administration of 100/xg SEB in BALB/c mice induced a massive synthesis of NO as indicated by high serum levels of nitrite (NO2−) and nitrate (NO3−) peaking 16 h after SEB injection. The inhibition of NO2− and NO3− release in mice injected with anti-tumor necrosis factor (TNF) and/or anti-interferon γ (IFN-γ) monoclonal antibody (mAb) before SEB challenge revealed that both cytokines were involved in SEB-induced NO overproduction. In vitro experiments indicated that NO synthase (NOS) inhibition by N-nitro-t-arginine methyl ester (L-NAME) enhanced IFN-γand TNF production by splenocytes in response to SEB. A similar effect was observed in vivo as treatment of mice with L-NAME resulted in increased IFN-γ and TNF serum levels 24 h after SEB challenge, together with persistent expression of corresponding cytokine mKNA in spleen. The prolonged production of inflammatory cytokines in mice receiving L-NAME and SEB was associated with a 95% mortality rate within 96 h, whereas all mice survived injections of SEB or t-NAME alone. Both TNF and IFN-γ were responsible for the lethality induced by SEB in L-NAME-treated mice as shown by the protection provided by simultaneous administration of anti-IFN-γ land anti-TNF mAbs. We conclude the SEB induces NO synthesis in vivo and that endogenous NO has protective effects in this model of T cell-dependent shock by downregulating IFN-γ and TNF production.

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