GASTRIN-SECRETION FROM PRIMARY CULTURES OF RABBIT ANTRAL G-CELLS - STIMULATION BY INFLAMMATORY CYTOKINES

Background & Aims: In Helicobacter pylori-induced gastritis, local pro duction of cytokines may favor hypergastrinemia as an endocrine link b etween H. pylori-induced gastritis and duodenal ulcer. The aim of this study was to characterize cytokine effects on cultured rabbit antral G cells. Methods: Monolayers (14.2% +/- 2.9% G cells) were studied aft er 48 hours in primary culture. Results: Interleukin (IL) 1 beta (50% effective concentration [EC(50)], 5.3 +/- 0.4 ng/mL) and tumor necrosi s factor (TNF) alpha (EC(50), 5.5 +/- 0.5 ng/mL) stimulated gastrin re lease to 50% of the maximal response to 10(-9) mol/L neuromedin C. Sti mulation by the maximally effective concentration of IL-1 beta (10 ng/ mL) was inhibited by the human IL-1 receptor antagonist (100 ng/mL inh ibitory constant, 23.0 ng/mL), which prefers type I over type II IL-1 receptors. The response to the maximally effective concentration of TN F-alpha (10 ng/mL) was markedly inhibited by monoclonal antibody H398, an antagonist at TNF P55 receptors (inhibitory constant, 1.7 mu g/mL) , whereas monoclonal antibody utr1, an antagonist at TNF P75 receptors , was ineffective, Stimulation by IL-1 beta and TNF-alpha was additive to the responses to neuromedin C and O-2-dibutyryl adenosine 3',5'-cy clic monophosphate. IL-6 and IL-8 (0.1-50 ng/mL) were ineffective, Con clusions: IL-1 beta and TNF-alpha stimulate gastrin secretion via rece ptors potentially residing on rabbit antral G cells themselves, We spe culate that 0 cells express type I IL-1 receptors and TNF P55 but not TNF P75 receptors.