Helicobacter pylori (H. pylori) infection is now recognized as the cause of type B gastritis, as a critical factor in the development and the recurrence of duodenal ulcer disease, and as an essential co-factor in the development of gastric carcinoma and gastric MALT-lymphoma^1–5). Although estimation of the lifetime risk of developing an ulcer in people with H. pylori infection is difficult, it is believed that approximatley 10 – 15 % of individuals with H. pylori infection may develop an ulcer.^{6, 7)} The link between H. pylori and the development of peptic ulcer disease may be related to the inappropriate release of gastrin observed in H. pylori-positive patients. One of the most notable H. pylori-associated changes in gastric secretion is an increased gastrin release after meals and after bombesin stimulation. This abnormality is alleviated following eradication of the infection^8–14). It has also been shown that H. pylori infection can induce reversible increased basal and gastrin mediated acid secretion^{15, 16)}.

The mechanism by which H. pylori enhances gastrin release is not yet known but there have been increasing numbers of studies which show that changes in the numbers of antral G-cells and D-cells are responsible for the physiologic regulation of gastrin and gastric acid secretion. Many of the studies have suggested that H. pylori infection results in reduction of the number of antral D-cells and in the soamatostatin level resulting in a lack of inhibition of G-cells which leads to an increased amount of gastrin in the antrum and the serum.17–19 The purpose of this study was to evaluate the influence of H. pylori infection on the behaviour of the G-cell and D-cell populations and on the relationship between the serum gastrin concentration and the G-cell to D-cell ratio.

Results are summarized in Table 1. There was no significant difference in the number of complete gastric gland profiles per field between patients with and without H. pylori infection. (9.8±2.7 vs 9.0±2.9, respectively, p>0.5).

The pathogenetic mechanism of H. pyori-associated peptic ulcer diseases have not been proved yet. However it is well known that a direct cytopathic effect of the organism on either the gastric or the duodenal epithelium is not involved in the development of peptic ulcer diseases because H. pylori is a non-invasive microorganism. One of the most characteristic abnormalities in gastric secretion induced by H. pylori infection is increased gastrin release after meals or after bombesin stimulation; this abnormality restored to its original state following eradication of the organism^8–14). It has also been shown that H. pylori infection can induce reversible increased both basal and gastrin-mediated acid secretion^{15, 16)}. However, the mechanism by which the microorganism alters gastrin metabolism is still unclear. Since synthesis and secretion of somatostatin, which is a physiologic paracrine inhibitor of antral G-cell function, are directly regulated by the intragastric pH, there is substantial evidence that the increased gastrin secretion of H. pylori-positive patients is related to an interplay between antral G-cells and D-cells. Therefore, we measured the numbers of antral G-cells and D-cells and correlated these numbers with serum gastrin concentrations in both H. pylori-infected and H. pylori-uninfected patients.

Our study showed that the number of complete gastric gland profiles was not different between patients with and without H. pylori infection. The number of G-cells per complete gastric gland was also not different between H. pylori-positive patients and -negative patients. Similar observations were made by Queiroz et al¹⁸⁾, Sankey et al²⁰⁾ and Moss et al²¹⁾, who demonstrated that the number of antral G-cells is apparently not affected by the presence of H. pylori. With regard to the serum gastrin concentration our results are in agreement with earlier studies which show that H. pylori-associated abnormalities in gastrin secretion are reversible with alleviation of the bacterial infection^{8–, 11, 13, 22–25)}.

There were also no differences in serum gastrin concentration between GU and DU patients within both the H. pylori-infected group and the H. pylori-uninfected group. In this study, the number of D-cells per complete gastric gland was significantly lower in both GU and DU patients with H. pylori infection compared to patients without infection. Consequently, the ratio of G-cells to D-cells was also significantly higher in H. pylori-positive patients than in H. pylori-negative patients. There were no differences in the ratio between GU and DU patients within both the H. pylori-infected group and H. pylori-uninfected group. Similar results have also been reported^{17, 18, 26, 27)}.

The mechanism by which H. pylori decreases the number of antral D-cells should be considered. One possible explanation is an inflammatory change in the region of the D-cells. Recently, Kaneko H. et al¹⁷⁾ and Moss et al¹⁹⁾ have reported that H. pylori infection is associated with a decrease in somatostatin-mRNA and is associated with the somatostatin-immunoreactive cell density of the antral mucosa. These changes were reversed after eradication of H. pylori. The degree of reversal was correlated with the grade of chronic inflammation. These findings are consistent with the reports of Domschke et al²⁸⁾ and Sumii et al²⁶⁾. Ito et al²⁹⁾ also reported that the number of D-cells decreased in proportion to the extent and degree of chronic atrophic gastritis, and that D-cells disappeared earlier and more diffusely than G-cells. Another possibilty may be a local alkaline environment induced by ammonia which is produced by bacterial urease. This possibility is supported by previous studies^30–34). These reports indicate that changes in intragastric acidity exert an influence on the antral D-cell density, on the tissue content of soamtostatin and on both the plasma and the antral gastrin concentration. Recently, there have been new efforts to explain the mechanism of increased gastrin release which is observed in patients with H. pylori infection. Graham et al³⁵⁾ observed that the number of G-cells was significantly lower in patients with DU than in either infected or uninfected controls, and that the ratio of G-cells to D-cells was similar in duodenal ulcer patients and in uninfected controls. They also found that, although eradication of the H. pylori infection results in a dramatic reduction in stimulated gastrin secretion, infection was not associated with a change in the number of either antral G-cells or D-cells in patients with DU. Based on these results they concluded that an H. pylori-associated increase in gastrin secretion appears to be related to local factors which regulate G-cell function. There are several reports regarding the role of cytokines, which are released by the inflammatory cells activated by H. pylori, in the regulation of antral G-cell function. These reports have suggested that interleukins, TNF-α or interferons stimulate gastrin secretion via receptors potentially residing on antral G-cells^36–38).

In conclusion, our results strongly suggest that the exaggerated response of gastrin secretion observed in H. pylori-positive patients is due to a reduction of the antral D-cell mass because these cells normally inhibit the synthesis and release of gastrin.