Effect of indomethacin on febrile response to recombinant human interleukin 1-alpha in rabbits

Effects of indomethacin, a potent inhibitor of prostaglandin (PG) synthesis, on the fever induced by recombinant human interleukin 1-alpha (rhIL 1-alpha) was studied in conscious rabbits. Intracerebroventricularly administered rhIL 1-alpha induced a dose-dependent increase in colonic temperature that was prominently suppressed by pretreatment with indomethacin given either intracerebroventricularly or subcutaneously. On the other hand, fever induced by intravenous administration of rhIL 1-alpha was not completely suppressed by either subcutaneous or intracerebroventricular indomethacin; a small rise in colonic temperature persisted at approximately 45 min after rhIL 1-alpha injection. This rise in colonic temperature was suppressed when indomethacin was given both intracerebroventricularly and subcutaneously. It is suggested that PGs synthesized in the central nervous system contribute to the IL 1 fever and that part of IL 1-alpha given peripherally is also transmitted into the central nervous system to contribute to IL 1 fever.