Tumour necrosis factor alpha stimulates gastrin release from canine and human antral G cells: possible mechanism of the Helicobacter pylori–gastrin link

There is evidence that gastric Helicobacter pylori ( Hp ) infection promotes duodenal ulceration by releasing gastrin. We therefore asked how Hp releases gastrin. Tumour necrosis factor alpha (TNF-α) is up-regulated in Hp gastritis and stimulates hormone release from pituitary cells, so we tested its effect on primary cultures of canine antral G cells and human antral fragments. TNF-α pretreatment (100ngmL^–1) of canine G cells significantly increased both basal (by 89%: P <0.01) and bombesin-stimulated (by 39% P <0.05) gastrin release. A similar pattern of increase was seen following TNF-α (20ngmL^?1) pretreatment of human antral fragments: basal gastrin release was increased by 38% ( P  < 0.05) and bombesin-stimulated by 26% ( P  < 0.05). This effect persisted during immunoblockade with anti-somatostatin antibody S6. We propose that TNF-α provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.