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Am J Physiol Gastrointest Liver Physiol (February 20, 2002). doi:10.1152/ajpgi.00422.2001
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Articles in PresS, published online ahead of print February 20, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00422.2001
Submitted on October 3, 2001
Accepted on February 5, 2002

IN SITU CORRELATION OF CYTOKINE SECRETION AND APOPTOSIS IN HELICOBACTER-ASSOCIATED GASTRITIS

Frank S Lehmann1*, Luigi M Terracciano2, Ilaria Carena3, Christian Baeriswyl2, Jurgen Drewe1, Luigi Tornillo4, Gennaro De Libero3, and Christian Beglinger1

1 Department of Gastroenterology, University of Basel, Basel, Switzerland
2 Institute of Pathology, University of Basel, Basel, Switzerland
3 Experimental Immunology, University of Basel, Basel, Switzerland
4 Department of Gastroenterology, University of Basel, Basel, Switzerland; Operative Unit of Pathology, Oncologic Regional Hospital, Rionero in Vulture, Italy

* To whom correspondence should be addressed. E-mail: falehmann{at}datacomm.ch.

TNF-{alpha} and IFN-{gamma} are important for the pathogenesis of H. pylori-associated gastritis and peptic ulcer disease. Gastric biopsies from Helicobacter pylori-positive and negative patients were used to examine the in situ correlation of TNF-{alpha} and IFN-{gamma} with epithelial cells 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 cells apoptosis (p<0.001) and Fas / Fas ligand expression (p<0.001). T cell lines and clones were all TCR {alpha}ß+ and showed Th1 functional phenotype. Using serial histological sections this study shows for the first time the in situ correlation of TNF-{alpha} and IFN-{gamma} with epithelial cells apoptosis, bacterial load and histological severity of disease and emphasizes the role of these cytokines in the pathophysiology of Helicobacter-associated disease.




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