Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1 beta

Background-In a previous study we showed that interleukin 1 beta (IL-1 beta ) caused recurrence of gastric ulcers in rats, and that adhesion molecules (intercellular adhesion molecule 1 and leucocytic beta2 integrins) play a r ole in this recurrence. Although gastric acid plays an important role in ma ny types of gastric injuries, including peptic ulcer recurrence, the mechan ism(s) remains unclear. Aims-To examine the involvement of gastric acid in induction of ulcer recur rence by IL-1 beta, and to investigate the role of gastric acid in inflamma tory responses during ulcer recurrence. Methods-Rats with healed ulcers were used. Rats were given 1 mug/kg IL-1 be ta intra-peritoneally. Another group of rats was given 20 mg/kg omeprazole for three days to inhibit acid secretion, and received IL-1 beta 20 hours a fter the first administration of omeprazole. They were then given 0.15 N HC l or vehicle at 0, 12, 24, and 36 hours after IL-1 beta treatment. Some rat s were given acid alone at the same time points. Expression of adhesion mol ecules was examined immunohistochemically and concentrations of IL-1 beta a nd tumour necrosis factor alpha (TNF-alpha) were measured by ELISA in scar tissue 24 hours after IL-L beta treatment. Results-IL-1 beta increased expression of adhesion molecules and concentrat ions of IL-1 beta and TNF-alpha in scar tissue by 24 hours after IL-1 beta treatment, and nine of 11 healed ulcers had recurred by 48 hours. Omeprazol e inhibited the effects of IL-1 beta. HCl acid abolished the inhibitory eff ects of omeprazole. Acid alone affected neither expression of adhesion mole cules nor cytokine concentrations, and did not cause recurrence. Conclusions-Gastric acid is required for recurrence of gastric ulcers cause d by IL-1 beta, and gastric acid stimulates the inflammatory process in sca rred mucosa during ulcer recurrence.