Inflammatory cytokines may affect cerebral circulation under pathological conditions. Responses of cerebral pial arterioles to one such cytokine, interleukin (IL)-1 beta and its inhibitor [soluble IL-1 receptor (sIL-1R)] were examined in anesthetized newborn pigs using closed cranial windows. Levels of prostanoids and cyclic nucleotides in periarachnoid cerebral spinal fluid (CSF) were measured. To examine the structure-activity relationship of the parent IL-1 beta molecule, two IL-1 beta fragments with amino acid sequences of 187-204 [IL-1 beta-(187-204)] and 208-240 [IL-1 beta-(208-240)] were tested for their effects on pial arterioles. Diameter changes of pial arterioles were sequentially recorded every 5 min for 30 min after topical application of IL-1 peptides. CSF was sampled at the end of the 30 min. IL-1 beta dose dependently induced arteriolar dilation and increased prostaglandin E2 (PGE2), 6-keto-PGF1 alpha adenosine 3',5'-cyclic monophosphate (cAMP), and guanosine 3',5'-cyclic monophosphate (cGMP). Intravenous indomethacin blocked the IL-1 beta-induced vasodilation, the increased prostanoids, and the increased cAMP, but not the increased cGMP. Neither heat-inactivated IL-1 beta nor IL-1 beta vehicle affected arteriolar diameter or CSF levels of prostanoids. The sIL-1R blocked the IL-1 beta-induced vasodilation and the increased CSF prostanoids. IL-1 beta-(208-240) also induced pial arteriolar dilation; however, its vasodilatory potency was 1,000 times less than that of the whole IL-1 beta molecule. IL-1 beta-(187-204) did not induce pial arteriolar dilation even when its dose was increased to the level of IL-1 beta-(208-240). These results suggest that IL-1 beta, through the activation of membrane-bound IL-1 beta receptors, induces pial arteriolar dilation via mechanisms that involve prostanoids and cyclic nucleotides. The results also indicate that the 208-240 amino acid sequence of IL-1 beta has a sequence-specific physiological function.