Potent inhibition of gastric acid secretion by intravenous interleukin-1 beta and -1 alpha in rats.
The influence of human and rat recombinant interleukin-1 (hIL-1 beta and -1 alpha and rIL-1 beta) on acid secretion was investigated in conscious pylorus-ligated rats. Intravenous injection of either hIL-1 beta, hIL-1 alpha or rIL-1 beta dose dependently inhibited gastric acid output with an ED50 of 0.05 microgram, 0.5 microgram and 2.2 micrograms, respectively. The antisecretory action of IL-1 beta was associated with an increase in circulating levels of gastrin. hIL-1 beta-induced inhibition of acid secretion was dose dependently reversed by peripheral injection of the IL-1 receptor antagonist, IL-RA, with a dose ratio of 1:10(3) for complete reversal. The inhibitory effect of hIL-1 beta was blocked by indomethacin and was not modified by IV injections of the CRF receptor antagonist, alpha-helical CRF(9-41), or the monoclonal somatostatin antibody CURE.S6, or by systemic capsaicin pretreatment. These results show that systemic hIL-1 beta-induced inhibition of gastric acid secretion is mediated through IL-1 receptors and prostaglandin pathways, and does not involves CRF receptors, afferent fibers, or changes in circulating gastrin or somatostatin levels.
Saperas
E
E
Center for Ulcer Research and Education, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Cominelli
F
F
Taché
Y
Y
D000818:Animals; D003346:Corticotropin-Releasing Hormone / Q000037:antagonists & inhibitors; D005744:Gastric Acid / Q000378:metabolism*; D006801:Humans; D007213:Indomethacin / Q000494:pharmacology; D007275:Injections, Intravenous; D007375:Interleukin-1 / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D010295:Parietal Cells, Gastric / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology
D007375:Interleukin-1; D011994:Recombinant Proteins; D003346:Corticotropin-Releasing Hormone; D007213:Indomethacin