Central action of recombinant interleukin-1 to inhibit acid secretion in rats

Abstract

The influence of recombinant human interleukins-1β and -1α and rat interleukin-1β on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1β, human interleukin-1α, or rat interleukin-1β induced a dose-dependent inhibition of gastric acid output. At IC doses < 100 ng, human interleukin-1β was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100–500 ng), human interleukins-1β and -1α and rat interleukin-1β were equipotent. The inhibitory effect was observed 30 minutes after interleukin-1 injection and maintained throughout the 6-hour experimental period. IC injection of interleukin-1β inhibited vagally stimulated gastric acid secretion induced by IC injection of the stable thyrotropin-releasing hormone analogue RX 77368. Indomethacin (1, 5, and 10 mg/ kg, IP, − 30 minutes) induced a dose-related prevention of the inhibitory effect of IC interleukin-1β. IC injection of the corticotropin-releasing factor antagonist α-CRF9-41, bilateral adrenalectomy, and noradrenergic blockade with bretylium did not influence the antisecretory effect of interleukin-1. Polypeptide action was not related to changes in circulating gastrin levels. Human interleukin-1β injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 103-fold higher than when given centrally. These results show that IC interleukin-1β acts centrally to induce a long-lasting inhibition of gastric acid secretion, and this effect requires the integrity of prostaglandin pathways. These data suggest a possible interaction between the immune and gastrointestinal systems.