BRAIN-TYPE-I BUT NOT TYPE-II IL-1 RECEPTORS MEDIATE THE EFFECTS OF IL-1-BETA ON BEHAVIOR IN MICE

In the immune system, interleukin (IL)-1 beta effects are mediated by the type I IL-1 receptors (IL-1RI), whereas the type II IL-1 receptors (IL-1RII) act as inhibitory receptors. IL-1RI and IL-1RII are also pr esent in the brain. To study their functionality in the brain, mice we re centrally treated with neutralizing monoclonal antibody (MAb) direc ted against IL-1RI (35F5, 1 mu g) or against IL-1RII (4E2, 2 mu g) and were centrally injected with recombinant rat IL-1 beta at a dose (2 n g) that decreased social exploration. Only 35F5 was effective in abrog ating the behavioral effect of IL-1 beta. Moreover, 4E2 (1 mu g icv) d id not potentiate the behavioral response to a subthreshold dose of IL -1 beta (1 ng icv). To examine the ability of brain IL-1RI to mediate the effects of endogenous IL-1 beta, mice were centrally treated with 35F5 (4 mu g) and peripherally injected with IL-1 beta (1 mu g). Like IL-1 receptor antagonist (4 mu g icy), 35F5 abrogated the effects of I L-1 beta. These results suggest that brain IL-1RI mediates the behavio ral effects of IL-1 beta in mice.