title: Staphylococcal enterotoxin A acts through nitric oxide synthase mechanisms in human peripheral blood mononuclear cells to stimulate synthesis of pyrogenic cytokines.
abstract: The pyrogenic response to supernatant fluids obtained from human peripheral blood mononuclear cells (PBMC) stimulated with staphylococcal enterotoxin A (SEA) was characteristic of a response to an endogenous pyrogen in that it was brief and monophasic and was destroyed by heating supernatant fluids at 70 degrees C for 30 min. The febrile responses were in parallel with the levels of interleukin-1 (IL-1), tumor necrosis factor (TNF), interferon-gamma (IFN-gamma), IL-2, and IL-6 in supernatant fluids obtained from PBMC treated with SEA. Both the pyrogenicity and the levels of IL-1, TNF, IFN-gamma, IL-2, and IL-6 in supernatant fluids started to rise at 6 to 18 h and reached their peak levels at 24 to 96 h after SEA incubation. Both the fever and the increased levels of IL-1, TNF, IFN-gamma, IL-2, and IL-6 in supernatant fluids obtained from the SEA-stimulated PBMC were decreased by incubating SEA-PBMC with anisomycin (a protein synthesis inhibitor), aminoguanidine (an inhibitor of inducible nitric oxide synthase [NOS]), or dexamethasone (an inhibitor of NOS). The febrile response to supernatant fluids obtained from the SEA-stimulated PBMC was attenuated by adding either anti-IL-1beta, anti-TNF-alpha, or anti-IFN-gamma monoclonal antibody (MAb) to supernatant fluids. The antipyretic effects exerted by anti-IL-1beta MAb were greater than those exerted by anti-TNF-alpha or anti-IFN-gamma MAb. The data suggest that SEA acts through the NOS mechanisms in PBMC to stimulate synthesis of pyrogenic cytokines (in particular, the IL-1beta).
authors.affiliation: Department of Microbiology, College of Medicine, National Cheng Kung University, Tainan, Taiwan.
authors.forename: S J
authors.initials: SJ
authors.lastname: Won
authors.forename: W T
authors.initials: WT
authors.lastname: Huang
authors.forename: Y S
authors.initials: YS
authors.lastname: Lai
authors.forename: M T
authors.initials: MT
authors.lastname: Lin
mesh_terms: D000818:Animals; D000841:Anisomycin / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D000893:Anti-Inflammatory Agents / Q000494:pharmacology; D000911:Antibodies, Monoclonal / Q000276:immunology; D016207:Cytokines / Q000096:biosynthesis*; D003907:Dexamethasone / Q000494:pharmacology; D004768:Enterotoxins / Q000378:metabolism* / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006801:Humans; D007371:Interferon-gamma / Q000096:biosynthesis / Q000276:immunology; D007375:Interleukin-1 / Q000096:biosynthesis / Q000276:immunology; D007376:Interleukin-2 / Q000096:biosynthesis; D015850:Interleukin-6 / Q000096:biosynthesis; D007963:Leukocytes, Mononuclear / Q000201:enzymology* / Q000382:microbiology*; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D011749:Pyrogens / Q000096:biosynthesis*; D011817:Rabbits; D013696:Temperature; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis / Q000276:immunology
chemical_list: D000900:Anti-Bacterial Agents; D000893:Anti-Inflammatory Agents; D000911:Antibodies, Monoclonal; D016207:Cytokines; D004768:Enterotoxins; D004791:Enzyme Inhibitors; D006146:Guanidines; D007375:Interleukin-1; D007376:Interleukin-2; D015850:Interleukin-6; D011749:Pyrogens; D014409:Tumor Necrosis Factor-alpha; C026066:enterotoxin A, Staphylococcal; D000841:Anisomycin; D003907:Dexamethasone; D007371:Interferon-gamma; D019001:Nitric Oxide Synthase; C004479:pimagedine