anisomycin and pimagedine

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).

Topics: Animals; Anisomycin; Anti-Bacterial Agents; Anti-Inflammatory Agents; Antibodies, Monoclonal; Cytokines; Dexamethasone; Enterotoxins; Enzyme Inhibitors; Guanidines; Humans; Interferon-gamma; Interleukin-1; Interleukin-2; Interleukin-6; Leukocytes, Mononuclear; Male; Nitric Oxide Synthase; Pyrogens; Rabbits; Temperature; Time Factors; Tumor Necrosis Factor-alpha

The febrile responses induced by i.v. administrations of staphylococcal enterotoxin A (SEA) was mimicked by direct injection of SEA into the organum vasculosum laminae terminalis (OVLT) in unanesthetized rabbits. Compared with the febrile responses induced by i.v. injection of SEA, the OVLT route of injection required a much lower dose of SEA to produce a similar fever. Furthermore, the fever induced by intra-OVLT or i.v. injection of SEA was significantly attenuated by pretreatment with intra-OVLT injection of anisomycin (a protein synthesis inhibitor), indomethacin or diclofenac (inhibitors of cyclo-oxygenase (COX)), and aminoguanidine or dexamethasone (inhibitors of inducible nitric oxide synthase (iNOS)). These results suggest that COX or iNOS pathway in the OVLT mediate the SEA-induced fever in rabbits.

Topics: Animals; Anisomycin; Cyclooxygenase Inhibitors; Dexamethasone; Diclofenac; Enterotoxins; Enzyme Inhibitors; Guanidines; Indomethacin; Injections, Intraventricular; Male; Nitric Oxide Synthase; Protein Synthesis Inhibitors; Pyrogens; Rabbits; Staphylococcus aureus; Superantigens