Acid regulates inflammatory response in a rat model of induction of gastric ulcer recurrence by interleukin 1β
- Dr T Watanabe, Department of Biosignal Analysis, Osaka City University Medical School, 1-4-3 Asahimachi, Abeno-ku, Osaka 545-8585, Japan.
- Accepted 21 July 2000
BACKGROUND In a previous study we showed that interleukin 1β (IL-1β) caused recurrence of gastric ulcers in rats, and that adhesion molecules (intercellular adhesion molecule 1 and leucocytic β2 integrins) play a role in this recurrence. Although gastric acid plays an important role in many types of gastric injuries, including peptic ulcer recurrence, the mechanism(s) remains unclear.
AIMS To examine the involvement of gastric acid in induction of ulcer recurrence by IL-1β, and to investigate the role of gastric acid in inflammatory responses during ulcer recurrence.
METHODS Rats with healed ulcers were used. Rats were given 1 μg/kg IL-1β intraperitoneally. Another group of rats was given 20 mg/kg omeprazole for three days to inhibit acid secretion, and received IL-1β 20 hours after the first administration of omeprazole. They were then given 0.15 N HCl or vehicle at 0, 12, 24, and 36 hours after IL-1β treatment. Some rats were given acid alone at the same time points. Expression of adhesion molecules was examined immunohistochemically and concentrations of IL-1β and tumour necrosis factor α (TNF-α) were measured by ELISA in scar tissue 24 hours after IL-1β treatment.
RESULTS IL-1β increased expression of adhesion molecules and concentrations of IL-1β and TNF-α in scar tissue by 24 hours after IL-1β treatment, and nine of 11 healed ulcers had recurred by 48 hours. Omeprazole inhibited the effects of IL-1β. HCl acid abolished the inhibitory effects of omeprazole. Acid alone affected neither expression of adhesion molecules nor cytokine concentrations, and did not cause recurrence.
CONCLUSIONS Gastric acid is required for recurrence of gastric ulcers caused by IL-1β, and gastric acid stimulates the inflammatory process in scarred mucosa during ulcer recurrence.
- Abbreviations used in this paper:
- tumour necrosis factor
- intercellular adhesion molecule 1
- lymphocyte function associated antigen 1
- proton pump inhibitor