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 E₂ (PGE₂), interferon (IFN)-γ, and interleukin (IL)-4 were determined in gastric biopsies before and after therapy. Histology was evaluated. RESULTS: Cyclooxygenase-2 expression and PGE₂ production was higher, and Th1 signaling pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet expression and IFN-γ 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.
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 E₂ (PGE₂), interferon (IFN)-γ, and interleukin (IL)-4 were determined in gastric biopsies before and after therapy. Histology was evaluated. RESULTS:Cyclooxygenase-2 expression and PGE₂ production was higher, and Th1 signaling pathway was predominant in H. pylori-infected vs. uninfected patients. T-bet expression and IFN-γ 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.
Authors: Hong Li; Matthew L Edin; Artiom Gruzdev; Jennifer Cheng; J Alyce Bradbury; Joan P Graves; Laura M DeGraff; Darryl C Zeldin Journal: Prostaglandins Other Lipid Mediat Date: 2012-11-28 Impact factor: 3.072