Helicobacter pylori infection and tumour necrosis factor-alpha increase gastrin release from human gastric antral fragments.
OBJECTIVE
To investigate the mechanism of the hypergastrinaemia associated with Helicobacter pylori infection by examining the effect of H. pylori infection and the cytokine tumour necrosis factor-alpha (TNF-alpha) on gastrin release from human antral fragments.


METHODS
In-vitro experimental study.


METHODS
Human antral biopsy fragments were cultured for 6 h with and without TNF-alpha (20 ng/ml) and the gastrin released over the following 2-h stimulation period measured by radioimmunoassay. The integrity of the paracrine feedback loop inhibiting gastrin release was tested by concurrent administration of cholecystokinin (CCK).


RESULTS
H. pylori-positive fragments were associated with significantly greater bombesin-stimulated gastrin release (increased by 40%, P < 0.05) and less inhibition produced by CCK administration (decreased by 55%, P < 0.05), than H. pylori-negative fragments. TNF-alpha treatment of H. pylori-negative fragments significantly enhanced bombesin-stimulated gastrin release (by 82%, P < 0.01) and diminished inhibitory feedback by CCK (by 53%, P < 0.05).


CONCLUSIONS
H. pylori infection is associated with enhanced gastrin release from human antrum and TNF-alpha produces a similar effect. Proinflammatory cytokines generated in the antrum in response to the infection are likely to play a significant role in the hypergastrinaemia of H. pylori infection.
Beales
I L
IL
Department of Gastroenterology, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Calam
J
J
D001839:Bombesin / Q000494:pharmacology; D002766:Cholecystokinin / Q000494:pharmacology; D005753:Gastric Mucosa / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D005755:Gastrins / Q000032:analysis / Q000378:metabolism*; D016481:Helicobacter Infections / Q000503:physiopathology*; D016480:Helicobacter pylori; D006801:Humans; D066298:In Vitro Techniques; D011706:Pyloric Antrum / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D011863:Radioimmunoassay; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D005755:Gastrins; D014409:Tumor Necrosis Factor-alpha; D002766:Cholecystokinin; D001839:Bombesin