Interaction of Helicobacter pylori eradication and non-steroidal anti-inflammatory drugs on gastric epithelial apoptosis and proliferation:: implications on ulcerogenesis

Background: Apoptosis is associated with loss of gastric mucosal integrity and may play an important role in ulcer development. Aim: To examine how Helicobacter pylori and NSAIDs interact to effect apoptosis and proliferation of the gastric mucosa. Methods: Patients presenting with musculoskeletal pain requiring NSAID treatment and without previous exposure to NSAID or pre-existing ulcers were recruited. Patients were divided into three groups: (A) H. pylori-infected; (B) H. pylori-eradicated; and (C) non-infected patients. They were given naproxen for 8 weeks. Patients with non-ulcer dyspepsia and H. pylori infection who were given anti-Helicobacter therapy were recruited as controls (D). Endoscopy was performed at baseline and 8-weeks after receiving naproxen. Gastric antral biopsies were obtained to assess apoptosis by terminal uridine deoxynucleotidyl nick end-labelling (TUNEL) and proliferation by Ki67 immunostaining. Results: A total of 55 patients were studied. H. pylori-positive patients had a higher apoptosis and proliferation index at baseline than non-infected patients (P < 0.0001), and eradication of H. pylori resulted in a significant reduction in these parameters. The NSAID induced apoptosis in non-infected subjects (P=0.03) whilst apoptosis was reduced in H. pylori-positive patients receiving NSAID (P=0.02). After 8 weeks of NSAID, post-treatment apoptosis was significantly higher in patients with persistent H. pylori infection than in non-infected patients (P=0.01). Conclusions: Eradication of H. pylori prior to NSAID therapy significantly reduces the level of apoptosis in the gastric mucosa, which may contribute to maintaining mucosa integrity and preventing ulcer development.