Protective effects of niacinamide in staphylococcal enterotoxin-B-induced toxicity.

Staphylococcal enterotoxins (SE) interact with major histocompatibility complex (MHC) class II cell-surface receptors, eliciting signal transduction in antigen-presenting cells (APC). Subsequent toxin-class II complex interaction with specific T-cell receptors induces T-cell activation. We investigated the effect of niacinamide and interleukin (IL)-10 on SEB-induced responses. In a macrophage cell line, niacinamide (ED50--2mM) and IL-10 (ED50--7U/ml) inhibited interferon (IFN)-gamma-induced MHC class II expression in a dose-dependent manner. Also, niacinamide was a potent inhibitor of T-cell proliferation induced by SEB (ED50-- 1 mM) while IL-10 has minimal effects. In mice, the temporal responses of IL-1alpha, tumor necrosis factor (TNF)-alpha, IL-2, and IFN-gamma evoked by SEB were synergistically potentiated by lipopolysaccharide (LPS). Lethality occurred only when SEB was potentiated by LPS. Niacinamide or IL-10 improved survival of mice after lethal SEB 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-1alpha and TNF-alpha. The immunomodulatory effects of niacinamide observed on SEB-induced 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.