PROTECTIVE EFFECTS OF NIACINAMIDE IN STAPHYLOCOCCAL ENTEROTOXIN-B-INDUCED TOXICITY

Staphylococcal enterotoxins (SE) interact with major histocompatibilit y complex (MHC) class II cell-surface receptors, eliciting signal tran sduction in antigen-presenting cells (APC). Subsequent toxin-dass II c omplex interaction with specific T-cell receptors induces T-cell activ ation. We investigated the effect of niacinamide and interleukin (IL)- 10 on SEB-induced responses. In a macrophage cell line, niacinamide (E D(50) - 2 mM) and IL-10 (ED(50) - 7 U/ml) inhibited interferon (IFN)-g amma-induced MHC class II expression in a dose-dependent manner. Also, niacinamide was a potent inhibitor of T-cell proliferation induced by SEB (ED(50) - 1 mM) while IL-10 had minimal effects. In mice, the tem poral responses of IL-1 alpha, tumor necrosis factor (TNF)-alpha, IL-2 , and IFN-gamma evoked by SEB were synergistically potentiated by lipo polysaccharide (LPS). Lethality occurred only when SEB was potentiated by LPS. Niacinamide or IL-10 improved survival of mice after lethal S EB challenge. Niacinamide reduced cytokine serum levels, although the pattern differed from that of IL-10. Niacinamide primarily reduced IL- 2 and IFN-gamma, while IL-10 predominantly reduced IL-1 alpha and TNF- alpha. The immunomodulatory effects of niacinamide observed on SEB-ind uced activation of APC and T-cells in vitro and in the LPS potentiated murine model for SEB-induced toxicity suggest it may have therapeutic value.