Short-term Therapy with Celecoxib and Lansoprazole Modulates Th1/Th2 Immune Response in Human Gastric Mucosa

Background: Selective cyclooxygenase-2 (COX-2) inhibitors and proton pump inhibitors may exert immune-mediated effects in human gastric mucosa. T-cell immune response plays a role in Helicobacter pylori-induced pathogenesis. This study evaluated effects of celecoxib and lansoprazole on T-helper (Th) 1 and Th2 immune response in human gastric mucosa. Methods: Dyspeptic patients with or without osteoarticular pain were given one of the following 4-week therapies: celecoxib 200 mg, celecoxib 200 mg plus lansoprazole 30 mg, and lansoprazole 30 mg daily. Expression of COX-2, T-bet, and pSTAT6 and production of prostaglandin E(2) (PGE(2)), interferon (IFN)-gamma, and interleukin (IL)-4 were determined in gastric biopsies before and after therapy. Histology was evaluated. Results: Cyclooxygenase-2 expression and PGE(2) production was higher, and Th1 signaling pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet expression and IFN-gamma production increased, while STAT6 activation and IL-4 production decreased following therapy with celecoxib and celecoxib plus lansoprazole, respectively. Th1 and Th2 signaling pathways down-regulated after therapy with lansoprazole, and this was associated with an improvement of gastritis. Effect of therapy was not affected by H. pylori status. Conclusion: Celecoxib and lansoprazole modulate Th1/Th2 immune response in human gastric mucosa. The use of these drugs may interfere with long-term course of gastritis.