ROLE OF INTERLEUKIN-8 ON LEUKOCYTE-ENDOTHELIAL CELL-ADHESION IN INTESTINAL INFLAMMATION

Background-An important action of interleukin 8 (IL8) is stimulation o f granulocytes. The object of this study was to assess the contributio n of IL8 to the leucocyte-endothelial cell interactions associated wit h intestinal inflammation in the rat. Methods Two indomethacin injecti ons (48 and 24 hours prior to the experiments) induced a longlasting i leitis in rats. The number of adherent and emigrated leucocytes, leuco cyte rolling velocity, and shear rate were monitored in normal and inf lamed mesenteric postcapillary venules. Some animals received a monocl onal 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 emigratio n, while leucocyte rolling velocity was reduced by nearly 80%. The ind omethacin 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 tha t associated with administration of a MAb directed against the leucocy te adhesion molecule CD11b/CD18. Conclusions-IL8 contributes to the le ucocyte-endothelial cell interactions elicited in mesenteric venules b y indomethacin.