INDOMETHACIN BLOCKS THE FEBRILE RESPONSE INDUCED BY INTERLEUKIN-8 IN RABBITS

Interleukin (IL)-8 induces fever in rats by a mechanism independent of the release of cyclooxygenase products. The purpose of this study was to investigate whether a similar mechanism is responsible for the pyr ogenic effect of IL-8 in rabbits. Intravenous (0.31-5.0 ng/kg) or intr acerebroventricular (15.6-250 pg) injections of IL-8 induced a dose-de pendent increase in body temperature. The correlations between the dos es of recombinant human IL-8 and the fever index were 0.98 and 0.99 fo r the intravenous and intracerebroventricular injections, respectively . The pyrogenic activity of IL-8 was not due to contamination with lip opolysaccharide (LPS), inasmuch as the Limulus amoebocyte lysate test showed <10 pg endotoxin/mu g IL-8, and boiled IL-8 lost its pyrogenic activity. Indomethacin (2 and 5 mg/kg ip) abolished the febrile respon se induced by the intravenous injection of LPS (5.0 ng/kg), IL-1 beta (5 ng/kg), and IL-8 (5 ng/kg). Indomethacin also abolished the fever i nduced by the intracerebroventricular injection of IL-8 (62.5 pg) but only partially reduced the response induced by the injection of IL-1 b eta (25 pg icv). These results show that, different from rats, indomet hacin blocks the febrile response induced by the central or peripheral administration of IL-8 in rabbits.