ENDOGENOUS GLUCOCORTICOIDS DOWN-REGULATE CENTRAL EFFECTS OF INTERLEUKIN-1-BETA ON BODY-TEMPERATURE AND BEHAVIOR IN MICE

Adrenalectomy sensitizes laboratory animals to the pyrogenic and behav ioural effects of proinflammatory cytokines. To determine whether thes e effects are mediated by central sites of action of glucocorticoids, interleukin-lp was injected intracerebroventricularly (i.c.v.) in adre nalectomized mice with or without corticosterone supplementation and i n mice pretreated i.c.v. with the glucocorticoid type II receptor anta gonist RU38486. Adrenalectomized mice were more sensitive to the depre ssing effects of i.c.v. IL-1 beta on body temperature and social explo ration than sham-operated mice. Corticosterone supplementation reverse d the increased sensitivity to the low (300 pg/mouse) but not to the h igh dose (900 pg/mouse) of IL-1 beta. Central administration of RU3848 6 (0.5-1 mu g/mouse) mimicked the effects of adrenalectomy on behaviou r but not on body temperature. These results suggest that endogenous g lucocorticoids released in response to IL-1 beta act in the brain to m odulate the sensitivity of the cellular targets of this cytokine.