Antiinflammatory effects of soluble complement receptor type 1 promote rapid recovery of ischemia/reperfusion injury in rat small intestine

We examined the effect of soluble complement receptor type I (sCR1) on muco sal injury and inflammation in a rat model of ischemia/reperfusion. Groups of vehicle- and sCR1-treated rats underwent 30 min of mesenteric ischemia f ollowed by 60 or 120 min of reperfusion. When compared to vehicle-treated r ats, treatment with sCR1 (12 mg/kg) prior to 120 min of reperfusion signifi cantly reduced mucosal injury, neutrophil infiltration, leukotriene B-4 pro duction, and restored villus height to control levels. The protective effec t of sCR1 evident at 120 min of reperfusion was not observed at 60 min of r eperfusion despite rapid inactivation of complement. These data suggest tha t complement inhibition minimized mucosal disruption by facilitating mucosa l restitution or interrupting the inflammatory process. Delayed administrat ion of sCR1 for 30 or 60 min into the reperfusion period progressively redu ced the protection. sCR1-mediated rapid recovery of rat intestine after isc hemia/reperfusion underscores the fundamental role of complement activation in neutrophil-mediated tissue injury.