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 behavioural effects of proinflammatory cytokines. To determine whether these effects are mediated by central sites of action of glucocorticoids, interleukin-lp was injected intracerebroventricularly (i.c.v.) in adrenalectomized mice with or without corticosterone supplementation and in mice pretreated i.c.v. with the glucocorticoid type II receptor antagonist RU38486. Adrenalectomized mice were more sensitive to the depressing effects of i.c.v. IL-1 beta on body temperature and social exploration than sham-operated mice. Corticosterone supplementation reversed the increased sensitivity to the low (300 pg/mouse) but not to the high dose (900 pg/mouse) of IL-1 beta. Central administration of RU38486 (0.5-1 mu g/mouse) mimicked the effects of adrenalectomy on behaviour but not on body temperature. These results suggest that endogenous glucocorticoids released in response to IL-1 beta act in the brain to modulate the sensitivity of the cellular targets of this cytokine.