OBJECTIVE: Helicobacter pylori-associated inflammation is mediated, in part, by inflammatory cytokines. In contrast, the mucosal disease associated with Zollinger-Ellison syndrome (ZES) is acid driven, and the role of cytokines is not known. The aim of this study was to elucidate the role of cytokines in these two diseases, as we quantitated proinflammatory cytokine messenger RNA (mRNA) levels in the gastric mucosa from patients with H. pylori infection and ZES. METHODS: The study population included 11 patients with H. pylori infection, 12 with ZES, 17 with both H. pylori infection and ZES, and three control subjects with neither. Using a competitive polymerase chain reaction for interleukin (IL)-1β, IL-6, IL-8, and tumor necrosis factor-α, the polymerase chain reaction products in gastric biopsies were quantitated by capillary electrophoresis and laser-induced fluorescence. RESULTS: The levels of IL-1β, IL-6, IL-8, and tumor necrosis factor-α mRNA in gastric tissue of patients with H. pylori infection only and ZES only exceeded the levels in the control gastric tissue (p < 0.05 to p < 0.005). Unexpectedly, the number of molecules of IL-1β and IL-8 mRNA in gastric tissue from ZES patients exceeded the levels in gastric tissue from patients with H. pylori only (p < 0.05). The local levels of cytokine mRNA in patients with both diseases exceeded the levels in patients with H. pylori only (IL-6, p < 0.05; IL-8, p < 0.05) and ZES only (IL-6, p < 0.05; tumor necrosis factor-α, p < 0.05). CONCLUSIONS: Levels of proinflammatory cytokine mRNA are increased in acid-driven as well as infection-driven gastric inflammation, and the presence of both disease processes appears to have an additive effect on local cytokine message expression. Inflammatory cytokines may mediate both infection- and acid-driven gastric inflammation. © 2002 by Am. Coll. of Gastroenterology.