Gastroenterology

Gastroenterology

Volume 109, Issue 4, October 1995, Pages 1173-1180
Gastroenterology

Indomethacin-induced gastric injury and leukocyte adherence in arthritic versus healthy rats

https://doi.org/10.1016/0016-5085(95)90576-6Get rights and content

Abstract

Background & Aims: Arthritic patients are at greater risk of developing nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers than other NSAID users. Leukocyte adherence to the vascular endothelium has been suggested to play an important role in the pathogenesis of experimental NSAID-associated gastropathy. The aim of this study was to examine the role of leukocyte adherence in NSAID-induced gastric injury in healthy and adjuvant-induced arthritic rats. Methods: Leukocyte adherence was examined using intravital microscopy before and after indomethacin administration. The role of CD18 and intercellular adhesion molecule 1 (ICAM-1) in indomethacin-induced gastric injury and leukocyte adherence was examined using specific monoclonal antibodies against these molecules. Results: Indomethacin (5–10 mg/kg) caused significantly more gastric damage in arthritic than normal rats, and the former group had significantly greater levels of leukocyte adherence to mesenteric postcapillary venules under basal conditions. Dexamethasone markedly reduced basal and indomethacin-induced leukocyte adherence and the extent of gastric damage. In arthritic rats, pretreatment with a monoclonal antibody directed against ICAM-1 significantly reduced gastric damage and leukocyte adherence to the levels observed in healthy rats, whereas an antibody directed against CD18 had no effect. Conclusions: Indomethacin-induced damage in healthy and arthritic rats is largely dependent on ICAM-1 expression. The increased susceptibility of arthritic rats to indomethacin-induced gastric injury may be partly related to elevated levels of ICAM-1-dependent leukocyte adherence.

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    Supported by a grant from the Medical Research Council of Canada (MRC). Dr. Wallace is an MRC Scientist and an Alberta Heritage Foundation for Medical Research (AHFMR) Scientist. Dr. McCafferty is an AHFMR Fellow.

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