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

Aliment Pharmacol Ther. 1999 Dec;13(12):1653-61. doi: 10.1046/j.1365-2036.1999.00670.x.


Background: Helicobacter pylori infection is associated with increased production of gastric mucosal reactive oxygen metabolites which have been implicated in mucosal damage and carcinogenesis. In vitro, neutrophils produce reactive oxygen metabolites following activation by H. pylori. Non-steroidal anti-inflammatory drugs (NSAIDs) inhibit neutrophil activation by several factors, e.g. N-formyl-methionyl-leucyl-phenyalanine (f-MLP).

Aim: To examine the effect of NSAIDs on H. pylori-induced reactive oxygen metabolite production by human peripheral blood neutrophils.

Methods: Neutrophils were stimulated by H. pylori (NCTC 11637) water extract 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 chemiluminescence which was inhibited dose-dependently by diclofenac. All six NSAIDs studied (at 10-4 M) significantly inhibited H. pylori-and f-MLP-stimulated neutrophil reactive oxygen metabolite production. Meclofenamic acid and diclofenac had the greatest inhibitory effects on both H. pylori and f-MLP-stimulated neutrophil reactive oxygen metabolite production. The inhibitory effects of other NSAIDs varied with the activation stimulus. NSAIDs did not quench reactive oxygen metabolites generated in a cell-free xanthine:xanthine 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.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Anti-Inflammatory Agents, Non-Steroidal / pharmacology*
  • Diclofenac / pharmacology
  • Dose-Response Relationship, Drug
  • Helicobacter pylori / physiology*
  • Humans
  • In Vitro Techniques
  • Luminescent Measurements
  • Lymphocyte Activation / drug effects
  • Male
  • Meclofenamic Acid / pharmacology
  • N-Formylmethionine Leucyl-Phenylalanine / pharmacology
  • Neutrophils / metabolism*
  • Reactive Oxygen Species / metabolism*
  • Time Factors
  • Xanthine Oxidase / metabolism
  • Xanthines / chemistry


  • Anti-Inflammatory Agents, Non-Steroidal
  • Reactive Oxygen Species
  • Xanthines
  • Diclofenac
  • Meclofenamic Acid
  • N-Formylmethionine Leucyl-Phenylalanine
  • Xanthine Oxidase