EFFECT OF SELECTIVE CYCLOOXYGENASE (COX)-2 INHIBITION AND PROTON PUMP INHIBITORS (PPI) THERAPY ON TH1 IMMUNE RESPONSE IN HUMAN GASTRIC MUCOSA

Background and aim: Helicobacter pylori colonizes the stomach of humans and causes gastritis, peptic ulcer, and gastric cancer. Evidences suggest that an impaired T cell response against H. pylori plays a role in the pathogenesis of H. pylori-related diseases. This study aimed at evaluating the effect of selective COX-2 inhibition therapy and PPI therapy on Th1 immune response in human gastric mucosa of H. pylori-infected and uninfected subjects. Material and methods: Patients who underwent esofagogastroduodenoscopy (EGDS) for dyspeptic symptoms and who suffered from osteoarticular pain were considered for the study. Three therapeutic regimens were planned: 1. celebrex 200 mg daily; 2. PPI at standard dose daily; 3. celebrex 200 mg plus a PPI at standard dose daily. Thirty-seven patients (median age 52 yrs, range 23-78) who underwent EGDS with biopsies at entry and after 4 week therapy were enrolled. The expression of COX-2, T-bet, and pSTAT6 along with the production of prostaglandin E2 (PGE2), IFN-gamma, and IL-4 were determined in total proteins extracted from freshly obtained gastric biopsies by western blotting and enzyme-linked immunosorbent assay (ELISA), respectively. A C13-urea breath test was performed to ascertain H. pylori status. Results: At baseline, it was confirmed that the expression of COX-2 and the production of PGE2 was higher and Th1 signalling pathway predominant in H. pylori-infected (n=23) compared to uninfected (n=14) patients. An enhanced expression of T-bet along with an increased production of IFN-gamma was observed in patients who had taken celebrex (n=7). Instead, PPI therapy downregulated Th1 and Th2 signalling pathways (n=18). Otherwise, no significant changes in Th1 signalling pathway were observed in patients who had taken celebrex plus PPI (n=12). H. pylori status did not significantly affect COX-2 and PPI induced changes. Conclusions: These data indicate that COX-2 selective inhibition and PPI therapy may interfere with normal T-cell activation in human gastric mucosa. In particular, the use of these drugs as immunomodulators in the course of H. pylori-induced gastric inflammatory changes deserves investigations. # B. Gastric diseases 4. H. Pylori/diagnosis/therapy