Abstract

Interleukin-1 (IL-1) and tumor necrosis factor-alpha (TNF-alpha) have been shown to inhibit basal and pentagastrin-stimulated gastric secretion in rats and histamine-stimulated secretion in dogs. IL-1 also reduces the severity of ethanol and stress-induced gastroduodenal damage. The aim of this study was to examine the effects of human recombinant IL-1 alpha and TNF-alpha on enzymatically dispersed and enriched (> 90%) parietal cells stimulated with histamine, histamine plus 3-isobutyl-1-methylxanthine (IMX) or carbachol (all 10(-5) M). Acid secretion was assessed indirectly by quantitating [14C]-aminopyrine (AP) accumulation. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine-stimulated AP uptake by 53% and 60% respectively, and it inhibited IL-1 alpha (1500 ng/ml) by 69%. IL-1 alpha (500 and 1000 ng/ml) inhibited histamine plus IMX-stimulated AP uptake by 36% and 34%, respectively. IL-1 alpha (500 ng/ml) also inhibited carbachol-stimulated AP accumulation. TNF-alpha (100 and 250 ng/ml) inhibited histamine-stimulated AP accumulation by 38% and 36%, respectively. TNF-alpha also significantly inhibited histamine/IMX- and carbachol-stimulated AP uptake (P < or = .01). Indomethacin did not affect IL-1 alpha-induced inhibition. These results show that IL-1 alpha and TNF-alpha inhibit histamine- and carbachol-stimulated isolated parietal cell secretion and that, for IL-1 alpha, this effect does not depend on mucosal prostaglandin synthesis.