Interleukin 1â and tumour necrosis factor á inhibit acid secretion in cultured rabbit parietal cells by multiple pathways

Background—The cytokines interleukin 1â (IL-1â) and tumour necrosis factor á (TNF-á) are inhibitors of gastric acid secretion when administered systemically. Aims—To investigate the inhibitory eVect of IL-1â and TNF-á on cultured, acid secreting parietal cells in order to determine the mechanism of this inhibition. Methods—Rabbit parietal cells were prepared by collagenase-EDTA digestion and counter flow elutriation. Acid secretory activity was assessed by aminopyrine accumulation. Results—IL-1â and TNF-á inhibited basal and stimulated acid secretion in a dose dependent manner; near maximal eVects were seen with both at 10 ng/ml. Inhibition was maximal with 15 minutes pretreatment but seen with up to 18 hours of preincubation. Both cytokines inhibited histamine, carbachol, gastrin, forskolin, and A23187 stimulated acid secretion but had no eVect on stimulation by dibutyrylcAMP. Inhibition of acid secretion was not accompanied by a change in radioligand binding to histamine H2 or gastrin/CCKB receptors. Pertussis toxin abolished the inhibitory eVects on histamine and forskolin stimulation. The tyrosine kinase inhibitor herbimycin reduced the inhibitory eVects of TNF-á against all stimuli but only reduced the eVects of IL-1â against histamine and forskolin stimulation. Conclusions—IL-1â and TNF-á seem to inhibit parietal cell acid secretion by multiple pathways; the inhibition occurs at postreceptor level and involves pertussis toxin and tyrosine kinase dependent and independent pathways. Mucosal production of cytokines may be important in the regulation of gastric acid secretion. (Gut 1998;42:227–234)