Interleukin-1beta (IL1beta) peripheral activities are mediated by type I IL1 receptors (IL1RI), whereas type II IL1 receptors (IL1RII) act as 'decoy' targets. To study the functionality of IL1RII in the brain, mice were treated with an intracerebroventricular injection of a neutralising MoAb directed against IL1RII (4E2, 1 microg) followed by recombinant rat IL1beta at a dose (2 ng) that produced a moderate but significant decrease of food intake 1 h 30 min after injection. The administration of 4E2 to IL-1beta treated mice significantly potentiated IL1beta-induced decrease in food intake without altering hypothermia. The effects of IL1beta were abrogated in the positive control group treated with IL1ra (2 microg, i.c.v). These results suggest that brain IL1RII down-regulate the effects of IL1beta on its cell targets in the brain.