Non-steroidal anti-inflammatory drugs inhibit Helicobacter pylori-induced human neutrophil reactive oxygen metabolite production in vitro

Background:Helicobacter pylori infection is associated with increased produ ction of gastric mucosal reactive oxygen metabolites which have been implic ated in mucosal damage and carcinogenesis. In vitro, neutrophils produce re active oxygen metabolites following activation by H. pylori. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil activation by several f actors, e.g. N-formyl-methionyl-leucyl-phenyalanine (f-MLP). Aim: To examine the effect of NSAIDs on H. pylori-induced reactive oxygen m etabolite production by human peripheral blood neutrophils. Methods: Neutrophils were stimulated by H. pylori (NCTC 11637) water extrac t or f-MLP in the presence or absence of NSAIDs. Reactive oxygen metabolite activity was measured by luminol-enhanced chemiluminescence. Results: H. pylori water extract stimulated a sevenfold increase in chemilu minescence which was inhibited dose-dependently by diclofenac. All six NSAI Ds studied (at 10(-4) M) significantly inhibited H. pylori-and f-MLP-stimul ated neutrophil reactive oxygen metabolite production. Meclofenamic acid an d diclofenac had the greatest inhibitory effects on both H. pylori and f-ML P-stimulated neutrophil reactive oxygen metabolite production. The inhibito ry effects of other NSAIDs varied with the activation stimulus. NSAIDs did not quench reactive oxygen metabolites generated in a cell-free xanthine:xa nthine oxidase assay. Conclusion: Several NSAIDs attenuate H. pylori-induced neutrophil reactive oxygen metabolites production in vitro. This may be relevant to a potential chemopreventative role in gastric cancer and to a possible lack of synergy between H. pylori and NSAID use regarding peptic ulceration.