Central interleukin-1 beta-induced inhibition of acid secretion in rats: specificity of action.
It is well established that IL-1 beta acts in the brain to potently inhibit gastric acid secretion in pylorus-ligated rats. The present study was designed to further investigate the specificity and mechanisms of the centrally mediated antisecretory action of IL-1 beta in conscious rats. Intracerebroventricular injection of IL-1 beta (100 ng) decreased acid secretion in pylorus-ligated rats and inhibited basal and pentagastrin-stimulated acid secretion in rats with chronic gastric fistula. The antisecretory effect of IL-1 beta (100 ng) injected into the lateral ventricle of pylorus ligated rats was completely reversed by prior intracerebroventricular injection of the IL-1 receptor antagonist, IL-1ra, (100 micrograms). Peripheral administration of the somatostatin monoclonal antibody, CURE.S6, did not modify intracisternal IL-1 beta-induced inhibition of acid secretion in pylorus ligated rats. IL-6 and tumor necrosis factor-alpha (100 ng) injected intracisternally did not influence gastric acid secretion in pylorus-ligated rats. These data show that IL-1 beta action in the CNS is mediated through interaction with specific IL-1 receptors and is selective to this cytokine. IL-1 beta antisecretory action can be observed under basal and pentagastrin-stimulated conditions and is independent from somatostatin release in the periphery.
Saperas
E
E
CURE/Digestive Disease Center, VA Wadsworth Medical Center, Los Angeles, CA 90073.
Taché
Y
Y
D000704:Analysis of Variance; D000818:Animals; D001921:Brain / Q000187:drug effects*; D002908:Chronic Disease; D005744:Gastric Acid / Q000378:metabolism*; D005747:Gastric Fistula / Q000503:physiopathology; D007276:Injections, Intraventricular; D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015850:Interleukin-6 / Q000494:pharmacology; D008026:Ligation; D008297:Male; D011708:Pylorus / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012795:Sialoglycoproteins / Q000494:pharmacology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D053590:Interleukin 1 Receptor Antagonist Protein; D007375:Interleukin-1; D015850:Interleukin-6; D012795:Sialoglycoproteins; D014409:Tumor Necrosis Factor-alpha