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-alpha) 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-alpha pretreatment (100 ng mL-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-alpha (20 ng mL-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-alpha provides the link between Hp infection and gastrin release and thus contributes to duodenal ulceration.