Intravenous interleukin-1-beta-induced inhibition of gastric emptying: involvement of central corticotrophin-releasing factor and prostaglandin pathways in rats.

The role of corticotrophin-releasing factor (CRF) and prostaglandin in interleukin-1 beta (IL-1 beta)-induced delayed gastric emptying was investigated. Gastric emptying was monitored 20 min after orogastric delivery of a methylcellulose phenol red solution in fasted rats injected intravenously with IL-1 beta at the ED50 dose (3 ng/rat) 30 min before the non-caloric solution. The IL-1 receptor antagonist (IL-1ra) injected intravenously (3 micrograms/rat) or intracisternally (100 ng/rat) reversed the IL-1 beta-induced 47% inhibition of gastric emptying by 100% and 62%, respectively. The new CRF antagonist [DPhe12, Nle21,38, C alpha MeLeu37]-CRF12-41 (20 micrograms/rat), injected intracisternally, or indomethacin (5 mg/kg i.p.) completely abolished IL-1 beta (3 ng/rat i.v.)-induced gastric stasis. The CRF antagonist injected intravenously (20 micrograms/rat) did not influence the IL-1 beta inhibitory action. None of the pretreatments given alone influenced basal gastric emptying. These data suggest that peripheral IL-1 beta-induced inhibition of gastric emptying is mediated by specific IL-1 receptor interactions and brain CRF pathways requiring the integrity of eicosanoid-cyclooxygenase pathways.