Anti-inflammatory and tissue-protectant drug effects: results from a randomized placebo-controlled trial of gastritis patients at high risk for gastric cancer

Background: The inflammatory process involving Helicobacter pylori-associat ed gastritis is thought to lead to epithelial damage and contribute to the development of gastric cancer. Evidence exists from animal and in vitro stu dies suggesting that tetracyclines have both anti-inflammatory and tissue-p rotectant effects unrelated to their antimicrobial activity. We attempted t o modulate components of H. pylori's inflammatory process by: (i) eliminati ng the infection; (ii) using tetracycline to alter the host's reaction to t he infection without reducing the bacterial load; and (iii) using calcium t o counteract the effect of excessive dietary salt. Methods: We conducted a 16-week placebo-controlled clinical trial with 374 H. pylori-associated gastritis patients randomly assigned to one of five gr oups: (1) triple therapy consisting of metronidazole, amoxicillin and bismu th subsalicylate for 2 weeks, followed by bismuth alone for 14 weeks; (2) c alcium carbonate; (3) triple therapy and calcium carbonate; (4) tetracyclin e; or (5) placebo. Results: Subjects in the tetracycline and triple therapy groups, but not th e calcium carbonate only group, showed a reduction in inflammation and epit helial damage vs. those in the placebo group, independent of a change in H. pylori density and other factors. Our results also indicate that epithelia l damage may be affected by mechanisms independent of H. pylori density or inflammation. Conclusion: The results are consistent with the hypothesis that tetracyclin e can decrease inflammation independent of a reduction in the bacterial loa d. More research is needed to investigate mechanisms leading to epithelial damage which are independent of H. pylori density and inflammation.