Selective COX-2 Inhibition Reduces Leukocyte Sticking and Improves the Microcirculation in TNBS Colitis

Abstract

The role of cyclooxygenase-2 inhibitors in the course of experimental colitis is controversially discussed. The aim of this study was to evaluate leukocyte-endothelium interaction and colitis activity after applying the selective cyclooxygenase-2 inhibitor NS-398 in a rat trinitrobenzene sulfonic acid (TNBS) colitis model. The acute phase of TNBS colitis is characterized by a significant reduction of capillary blood flow, capillary density, diuresis, and weight and a significant increase in capillary permeability, leukocyte sticking, and hematocrit. Applying the selective cyclooxygenase-2 inhibitor NS-398 leads to a significant improvement of all microcirculatory parameters and clinical findings compared to the (untreated) colitis group. There are no histopathological differences between the individual colitis groups. Acute colitis is characterized by an extensive disturbance of microcirculation together with signs of systemic inflammatory response syndrome. These alterations are significantly improved by inhibiting cyclooxygenase-2. The results support the described correlation between cyclooxygenase activation and leukocyte-endothelium interaction. Moreover, they underscore the postulated relation between leukocyte-endothelium interaction and capillary blood flow.