Interleukin 1β inhibits gastric emptying in rats: Mediation through prostaglandin and corticotropin-releasing factor

Background/Aims: Interleukin 1β (IL-1β) 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-1β on gastric emptying were investigated. Methods: 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-1β in conscious rats. Results: IL-1β 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-1β was injected intracisternally (0.1 ng) than intravenously (3 ng). The inhibitory effect of intracisternal IL-1β 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-1β (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, Nle21,38,CαMeLeu37]CRF12–41 (20 μg) prevented by 100% and 52%, respectively, the inhibition of gastric emptying evoked by intracisternal IL-1β (0.1 ng). The antagonists alone had no effect on basal gastric emptying. Conclusions: IL-1β acts in the brain to induce a long-lasting inhibition of gastric emptying; IL-1β action is mediated through central IL-1 receptors and prostaglandin- and CRF-dependent mechanisms.