Central action of recombinant interleukin-1 to inhibit acid secretion in rats.
The influence of recombinant human interleukins-1 beta and -1 alpha and rat interleukin-1 beta on gastric acid secretion was investigated in awake rats with pylorus ligation. IC injection of either human interleukin-1 beta, human interleukin-1 alpha, or rat interleukin-1 beta induced a dose-dependent inhibition of gastric acid output. At IC doses less than 100 ng, human interleukin-1 beta was more effective than the other forms or sources of interleukin-1, whereas at higher doses (100-500 ng), human interleukins-1 beta and -1 alpha and rat interleukin-1 beta 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-1 beta 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-1 beta. IC injection of the corticotropin-releasing factor antagonist alpha-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-1 beta injected IV also inhibited gastric acid secretion, but the peripheral dose required to induce a significant effect was 10(3)-fold higher than when given centrally. These results show that IC interleukin-1 beta 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.
Saperas
E S
ES
Center for Ulcer Research and Education, VA Wadsworth Medical Center, Los Angeles.
Yang
H
H
Rivier
C
C
Taché
Y
Y
D000818:Animals; D001921:Brain / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005744:Gastric Acid / Q000378:metabolism*; D007213:Indomethacin / Q000494:pharmacology; D007267:Injections; D007274:Injections, Intraperitoneal; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins; D013973:Thyrotropin-Releasing Hormone / Q000031:analogs & derivatives / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D013973:Thyrotropin-Releasing Hormone; C027979:L-pyroglutamyl-L-histidyl-3,3-dimethylprolinamide; D011761:Pyrrolidonecarboxylic Acid; D007213:Indomethacin