Helicobacter pylori infection and tolerance to H2 blockers

Abstract

Sirs, We appreciate Drs Zentilin, Savarino and Savarino's comments and their interest in our manuscript.1 Our study clearly demonstrated that Helicobacter pylori (H. pylori) infection prevents the tolerance phenomenon during the administration of H2 receptor antagonists (H2RAs). The lack of tolerance to H2RAs in subjects with H. pylori infection may explain the long-term efficacy of H2RAs for the maintenance therapy of peptic ulcer patients who have H. pylori infection.2–4 Our study, unfortunately, was not designed to clarify the mechanism responsible for this phenomenon. Therefore, the possible mechanism of the lack of tolerance to H2RA is beyond the scope of our study. However, several possible mechanisms may be pointed out. One of them is the decreased gastric acid secretion in patients with H. pylori infection partly because of the gastric mucosal atrophy and partly because of the H. pylori-induced production of anti-secretory cytokines including interleukin (IL)-1β.5H.pylori-infection may also decrease the gastric acidity by producing NH4+ and neutralizing secreted acid.6 Decreased acidity may inhibit the early occurrence of tolerance to H2RAs. Other possible mechanism is the H. pylori-induced alteration of parietal cell sensitivity to the acid-inhibition by H2RAs. As the number of H2 receptors on parietal cells was reported to increase significantly during the long-term administration of H2RAs,7H. pylori may change the number of H2 receptors or alter the intracellular signal transduction system coupled to H2 receptors in parietal cells resulting dysfunction of the tolerance mechanism. To clarify the precise mechanism through which tolerance phenomenon to H2RAs is blocked in cases of H. pylori infection, further in vivo and in vitro studies are necessary. Zentilin et al. speculated that not the gastric mucosal atrophy but the increased anti-secretory action of H2RAs may prevent the development of tolerance in H. pylori-infected individuals. As gastric mucosal atrophy was demonstrated to reflect serum pepsinogen levels,8 we have measured serum pepsinogen I and II concentrations of all the volunteers in our study. Serum pepsinogen I concentrations in H. pylori infected cases was not lower than those in non-infected subjects (Table 1). Therefore, we agree with Zentilin et al. that gastric mucosal atrophy may not be the primary mechanism of the lack of tolerance to H2RAs in our study population. To measure the sensitivity to the anti-secretory action of H2RAs, the plasma concentrations-based dose-dependent effect of H2RAs has to be investigated in volunteers. We expect to clarify the mechanism in our future study.