title: Interleukin-1 beta peptides induce cerebral pial arteriolar dilation in anesthetized newborn pigs.
abstract: 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.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163 USA.
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: S L
authors.initials: SL
authors.lastname: Zuckerman
authors.forename: J M
authors.initials: JM
authors.lastname: Seyer
authors.forename: J M
authors.initials: JM
authors.lastname: Krueger
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D015121:6-Ketoprostaglandin F1 alpha / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid; D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D015232:Dinoprostone / Q000037:antagonists & inhibitors / Q000134:cerebrospinal fluid; D007213:Indomethacin / Q000494:pharmacology; D007375:Interleukin-1 / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010841:Pia Mater / Q000098:blood supply*; D017472:Receptors, Interleukin-1 / Q000502:physiology; D012995:Solubility; D013552:Swine; D014664:Vasodilation
chemical_list: D007375:Interleukin-1; D010446:Peptide Fragments; D017472:Receptors, Interleukin-1; D015121:6-Ketoprostaglandin F1 alpha; D015232:Dinoprostone; D007213:Indomethacin