HOW DOES HELICOBACTER-PYLORI CAUSE MUCOSAL DAMAGE - ITS EFFECT ON ACID AND GASTRIN PHYSIOLOGY

Helicobacter pylori infection increases gastric acid secretion in pati ents with duodenal ulcers but diminishes acid output in patients with gastric cancer and their relatives. Investigation of the basic mechani sms may show how H. pylori causes different diseases in different pers ons. Infection of the gastric antrum increases gastrin release. Certai n cytokines released in H. pylori gastritis, such as tumor necrosis fa ctor alpha and specific products of H. pylori, such as ammonia, releas e gastrin from G cells and might be responsible. The infection also di minishes mucosal expression of somatostatin. Exposure of canine D cell s to tumor necrosis factor a in vitro reproduces this effect. These ch anges in gastrin and somatostatin increase acid secretion and read to duodenal ulceration. But the acid response depends on the state of the gastric corpus mucosa. The net effect of corpus gastritis is to decre ase acid secretion. Specific products of H. pylori inhibit parietal ce lls. Also, interleukin 1 beta, which is overexpressed in H. pylori gas tritis, inhibits both parietal cells and histamine release from entero chromaffin-like cells. H. pylori also promotes gastric atrophy, leadin g to loss of parietal cells. Factors such as a high-salt diet and a la ck of dietary antioxidants, which also increase corpus gastritis and a trophy, may protect against duodenal ulcers by decreasing acid output. However, the resulting increase of intragastric pH may predispose to gastric cancer by allowing other bacteria to persist and produce carci nogens in the stomach.