STAPHYLOCOCCAL-ENTEROTOXIN A-INDUCED FEVER IS ASSOCIATED WITH INCREASED CIRCULATING LEVELS OF CYTOKINES IN RABBITS

Rabbits were injected intravenously with 10 to 100 ng of staphylococca l enterotoxin A (SEA) per kg, and colonic temperatures were monitored. The febrile responses were compared with circulating levels of interf eron (IFN), tumor necrosis factor (TNF), interleukin-1 (IL-1), IL-2, a nd IL-6 just before the injection of SEA. Both colonic temperatures an d circulating levels of IFN, TNF, and IL-2 started to rise at 1 to 2 h and reached their peak levels at 3 to 5 h after SEA injection. Both t he fever and the increased circulating levels of IFN, TNF, and IL-2 pr oduced by SEA were decreased by pretreatment with indomethacin (a cycl o-oxygenase inhibitor) (15 mg/kg, intraperitoneally), anisomycin (a pr otein synthesis inhibitor) (15 mg/kg, subcutaneously), or dexamethason e (an effective anti-inflammatory and immunosuppressive agent) (4 mg/k g, intravenously) in rabbits, Rabbits were injected intravenously with 30 ng of SEA per kg on four consecutive days, and calonic temperature s were monitored. Compared to rabbits that received the single injecti on of SEG rabbits that received four consecutive injections of SEA sho wed a lesser increase in circulating levels of IFN, TNF, and IL-2 as w ell as colonic temperatures in response to an intravenous dose of SEA (30 ng/kg). The data suggest that the prevention of the febrile respon se elicited by SEA by indomethacin, anisomycin, or dexamethasone is du e to prevention hy these compounds of the increase in the circulating levels of IFN, TNF, and IL-2. The pyrogenic hyporesponsiveness to repe ated injection of SEA is associated with decreased production of these circulating cytokines.