Long-term use of nonsteroidal anti-inflammatory drugs normalizes the kinetics of gastric epithelial cells in patients with Helicobacter pylori infection via attenuation of gastric mucosal inflammation

Abstract

Helicobacter pylori (H. pylori) is associated with chronic gastritis and gastric carcinogenesis. The effects of nonsteroidal anti-inflammatory drugs (NSAIDs), which exert chemopreventive effects on several cancers, on H. pylori-induced gastritis remain unknown. We investigated the effects of NSAIDs on gastric inflammation and the kinetics of gastric epithelial cells in H. pylori-induced gastritis. Patients with rheumatoid arthritis or osteoarthritis who took NSAIDs for more than 1 month and complained of dyspeptic symptoms were recruited for this study. Patients not on any NSAIDs were included as non-NSAID user controls. All patients underwent diagnostic testing for H. pylori infection, esophagogastroduodenoscopy, and gastric biopsies. Neutrophil infiltration into gastric mucosa, expression of inducible nitric oxide synthase (iNOS), and apoptosis and proliferation of gastric epithelial cells were evaluated by immunohistochemistry. In an in vitro study, the effects of NSAIDs on production of interleukin (IL)-8 induced by H. pylori in a gastric epithelial cell line (AGS) were determined. Numbers of neutrophils infiltrating the gastric mucosa, iNOS-expressing inflammatory cells and apoptotic cells, and proliferating cells in gastric epithelium were higher in H. pylori-positive groups than H. pylori-negative groups. Among H. pyloripositive groups, these parameters were lower in NSAID users than in non-NSAID users. NSAIDs inhibited the production of IL-8 induced by H. pylori in AGS cells. These findings suggest that long-term use of NSAIDs normalizes the kinetics of gastric epithelial cells in patients with H. pylori infection by attenuating gastric mucosal inflammation, which may result in prevention of the gastric carcinogenesis associated with H. pylori infection.