INDOMETHACIN-INDUCED GASTRIC INJURY AND LEUKOCYTE ADHERENCE IN ARTHRITIC VERSUS HEALTHY RATS

Background & Aims: Arthritic patients are at greater risk of developin g nonsteroidal anti-inflammatory drug (NSAID)-induced ulcers than othe r NSAID users. Leukocyte adherence to the vascular endothelium has bee n suggested to play an important role in the pathogenesis of experimen tal NSAID-associated gastropathy. The aim of this study was to examine the role of leukocyte adherence in NSAID-induced gastric injury in he althy and adjuvant-induced arthritic rats. Methods: Leukocyte adherenc e was examined using intravital microscopy before and after indomethac in administration. The role of CD18 and intercellular adhesion molecul e 1 (ICAM-1) in indomethacin-induced gastric injury and leukocyte adhe rence was examined using specific monoclonal antibodies against these molecules. Results: Indomethacin (5-10 mg/kg) caused significantly mor e gastric damage in arthritic than normal rats, and the former group h ad significantly greater levels of leukocyte adherence to mesenteric p ostcapillary venules under basal conditions. Dexamethasone markedly re duced basal and indomethacin-induced leukocyte adherence and the exten t 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, where as an antibody directed against CD18 had no effect. Conclusions: Indom ethacin-induced damage in healthy and arthritic rats is largely depend ent on ICAM-1 expression. The increased susceptibility of arthritic ra ts to indomethacin-induced gastric injury may be partly related to ele vated levels of ICAM-1-dependent leukocyte adherence.