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.
LeClaire
R D
RD
United States Army Medical Research Institute of Infectious Diseases, Toxicology Divsion, Frederick, MD, USA.
Kell
W
W
Bavari
S
S
Smith
T J
TJ
Hunt
R E
RE
D000818:Animals; D002455:Cell Division / Q000187:drug effects; D002460:Cell Line; D016207:Cytokines / Q000097:blood; D004768:Enterotoxins / Q000633:toxicity*; D000949:Histocompatibility Antigens Class II / Q000096:biosynthesis; D007371:Interferon-gamma / Q000097:blood / Q000494:pharmacology; D016753:Interleukin-10 / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000633:toxicity; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D009536:Niacinamide / Q000494:pharmacology*; D014176:Protein Biosynthesis; D012333:RNA, Messenger / Q000096:biosynthesis; D012772:Shock, Septic / Q000188:drug therapy*; D013154:Spleen / Q000166:cytology / Q000378:metabolism; D013210:Staphylococcus; D015996:Survival Rate; D013601:T-Lymphocytes / Q000187:drug effects / Q000276:immunology; D013997:Time Factors
D016207:Cytokines; D004768:Enterotoxins; D000949:Histocompatibility Antigens Class II; D008070:Lipopolysaccharides; D012333:RNA, Messenger; D016753:Interleukin-10; D009536:Niacinamide; C031818:enterotoxin B, staphylococcal; D007371:Interferon-gamma