Effect of transforming growth factor alpha and interleukin 8 on somatostatin release from canine fundic D cells.

Helicobacter pylori infection in patients who have peptic ulcer disease is associated with altered regulation of gastric secretion, hypergastrinemia, and diminished somatostatin expression in gastric mucosa. Tumor necrosis factor (TNF)-alpha and interleukin (IL)-8 are the predominant cytokines produced in the gastric mucosa of patients with H. pylori infection. The aim of this study was to examine whether IL-8 and TNF-alpha could regulate somatostatin release from isolated canine gastric D cells. Canine gastric D cells were isolated from fundic mucosa and enriched by centrifugal elutriation. Secretagogue-stimulated somatostatin release was measured by radioimmunoassay. TNF-alpha dose dependently increased somatostatin release after 2 hours of treatment. The stimulatory effect of TNF-alpha was additive to that of epinephrine but was unaffected by a maximal concentration of cholecystokinin. IL-8 did not alter basal or secretagogue (cholecystokinin, epinephrine)-mediated somatostatin release. The stimulatory effect of TNF-alpha (10 ng/mL) was potentiated by the addition of IL-8 (1 nmol/L), inhibited by octreotide and staurosporine, but unaffected by indomethacin. Pretreatment of D cells with TNF-alpha (10 ng/mL) for 24 hours abolished the subsequent stimulatory effect of this cytokine and secretagogues on somatostatin release. TNF-alpha was shown to regulate somatostatin release from cultured D cells in a divergent manner.