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Am J Physiol Gastrointest Liver Physiol 283: G481-G488, 2002. First published February 20, 2002; doi:10.1152/ajpgi.00422.2001
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Vol. 283, Issue 2, G481-G488, August 2002

In situ correlation of cytokine secretion and apoptosis in Helicobacter pylori-associated gastritis

Frank Serge Lehmann1, Luigi Terracciano2, Ilaria Carena3, Christian Baeriswyl2, Jürgen Drewe1, Luigi Tornillo2,4, Gennaro De Libero3, and Christoph Beglinger1

1 Department of Gastroenterology, 2 Institute of Pathology, and 3 Department of Experimental Immunology, University Hospital of Basel, 4031 Basel, Switzerland, 4 Operative Unit of Pathology and Cytopathology, Regional Cancer Center, 85028 Rionero in Vulture, Italy

Tumor necrosis factor-alpha (TNF-alpha ) and interferon-gamma (IFN-gamma ) are important for the pathogenesis of Helicobacter pylori-associated gastritis and peptic ulcer disease. Gastric biopsies from H. pylori-positive and -negative patients were used to examine the in situ correlation of TNF-alpha and IFN-gamma with epithelial cell apoptosis, bacterial load, and histological parameters of gastritis. From the same patients, we isolated H. pylori-specific T cell lines and clones and examined their ex vivo release of proinflammatory cytokines. We found a highly significant correlation of TNF-alpha and IFN-gamma production with activity and grade of gastritis (P < 0.01), H. pylori density (P = 0.01), epithelial cell apoptosis (P < 0.001), and Fas/Fas-ligand expression (P < 0.001). T cell lines and clones were all TCR-alpha beta + and showed T helper 1 functional phenotype. With the use of serial histological sections, this study showed for the first time the in situ correlation of TNF-alpha and IFN-gamma with epithelial cell apoptosis, bacterial load, and histological severity of disease and emphasizes the role of these cytokines in the pathophysiology of H. pylori-associated disease.

tumor necrosis factor-alpha ; interferon-gamma ; Fas, Fas-ligand; human leukocyte antigen D-related


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