CORTICOSTERONE MODULATES INTERLEUKIN-EVOKED FEVER IN THE RAT

The role of endogenous corticoids in fever responses caused by recombi nant murine interleukin (IL)-1beta and IL-6 was studied in adult male Wistar rats. Adrenalectomy diminished the development of fever after i ntracerebroventricular (icv) injection of these ILs and lowered body t emperature. Intraperitoneal administration of the same doses of ILs di d not produce fever in intact animals or hypothermia in adrenalectomiz ed rats, thus suggesting a central site of action of IL-1beta and IL-6 in these experiments. Chronic replacement with moderate doses of cort icosterone restored the fever response in adrenalectomized animals in response to icv administration of IL-1beta but only partially reversed the fever caused by IL-6. Adrenalectomized animals acutely treated wi th corticosterone and thereafter with either IL-1beta or IL-6 develope d fever more rapidly than did chronically corticosterone-treated anima ls. In intact animals corticosterone blocked the fever response to icv injected IL-1beta. We propose that in the rat corticosterone acts in a bimodal manner on body temperature; it exerts a permissive central e ffect on the fever response and limits the production of inflammatory mediators in the brain. Conversely, higher corticosterone doses probab ly reduce the magnitude of the fever response.