Interleukin 1 beta inhibits gastric emptying in rats: mediation through prostaglandin and corticotropin-releasing factor.

Abstract

Interleukin 1 beta (IL-1 beta) increases the release of corticotropin-releasing factor (CRF) in the brain through prostaglandin pathways. Because central CRF inhibits gastric motor function, the influence and mechanism of action of intracisternal injection of IL-1 beta on gastric emptying were investigated. The 20-minute rate of gastric emptying of a nonnutrient test meal was assessed by the phenol red methylcellulose method 30 minutes after injection of human recombinant IL-1 beta in conscious rats. IL-1 beta injected intracisternally (0.01-1 ng) or intravenously (0.01-10 ng) dose-dependently decreased gastric emptying by 10%-82% and 0%-89%, respectively. The median effective dose (ED50) was 30-fold lower when IL-1 beta was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1 beta had a rapid onset (within 20 minutes) and was long-lasting (6 hours). Indomethacin (5 mg/kg, intraperitoneally) completely prevented the 61% inhibition induced by intracisternal IL-1 beta (0.1 ng) but had no effect on CRF-induced (600 ng) 72% inhibition of gastric emptying. The intracisternal injection of the IL-1 receptor antagonist (100 ng) or the CRF antagonist [DPhe12, [DPhe12,Nle21,38,C alpha MeLeu37]CRF12-41 (20 micrograms) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1 beta (0.1 ng). The antagonists alone had no effect on basal gastric emptying. IL-1 beta acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1 beta action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.