Central mediators involved in the febrile response induced by polyinosinic-polycytidylic acid: lack of involvement of endothelins and substance P.

The present study evaluated the involvement of interleukin(IL)-1ß, tumor necrosis factor-α (TNF-α), IL-6, interferon(IFN)-γ, prostaglandins of the E2 series, endothelins, substance P and opioids within the central nervous system in polyinosinic:polycytidylic acid (Poly I:C)-induced fever in rats. Poly I:C injection induced a febrile response which was reduced by intracerebroventricular administration of the antibodies against TNF-α, IL-6, or IFN-γ, or by IL-1 or µ receptor antagonists. Intraperitoneal injection of indomethacin or oral administration of celecoxib also reduced Poly I:C-induced fever. Poly I:C increased prostaglandin E2 levels in the cerebrospinal fluid of the animals which was also reduced by indomethacin. The intracerebroventricular injection of ETB or NK1 receptor antagonists did not alter Poly I:C-induced fever. These data suggest the involvement of IL-1ß, TNF-α, IL-6, IFN-γ, prostaglandin E2, and opioids but not endothelins and substance P on Poly I:C-induced fever.