Role of interleukin 8 on leucocyte-endothelial cell adhesion in intestinal inflammation

Abstract

Background - An important action of interleukin 8 (IL8) is stimulation of granulocytes. The object of this study was to assess the contribution of IL8 to the leucocyte-endothelial cell interactions associated with intestinal inflammation in the rat. Methods - Two indomethacin injections (48 and 24 hours prior to the experiments) induced a longlasting ileitis in rats. The number of adherent and emigrated leucocytes, leucocyte rolling velocity, and shear rate were monitored in normal and inflamed mesenteric postcapillary venules. Some animals received a monoclonal antibody (MAb) against IL8 or CD11b/CD18 at 24 and 12 hours prior to the experiment. Results - Indomethacin elicited a sevenfold increase in leucocyte adherence and a 5.4-fold increase in leucocyte emigration, while leucocyte rolling velocity was reduced by nearly 80%. The indomethacin induced increases in leucocyte adherence and emigration were significantly reduced (by 57% and 67%, respectively) while leucocyte rolling velocity was increased (to 63% of control) by the IL8- specific MAb. The level of inhibition seen with the IL8 MAb was similar to that associated with administration of a MAb directed against the leucocyte adhesion molecule CD11b/CD18. Conclusions - IL8 contributes to the leucocyte- endothelial cell interactions elicited in mesenteric venules by indomethacin.