PREVENTION OF SMALL-INTESTINAL ISCHEMIA-REPERFUSION INJURY IN RAT BY ANTI-CYTOKINE-INDUCED NEUTROPHIL CHEMOATTRACTANT MONOCLONAL-ANTIBODY

The function of cytokine-induced neutrophil chemoattractant (CINC), wh ich is the rat counterpart to human growth-related gene product belong ing to the CXC chemokine subgroup, is based principally on neutrophil- specific chemotactic activity. In addition, we previously reported tha t plasma CINC was elevated during the period of small intestinal ische mia-reperfusion injury, and that there was a correlation between the d egree of mucosal damage and the peak level of CINC after reperfusion, suggesting that CINC may play a major role in neutrophil infiltration into the rat small intestinal ischemia-reperfusion injury site. Thus, we investigated whether administration of anti-CINC monoclonal antibod ies (mAbs) reduces small intestinal ischemia-reperfusion injury. Small intestine was subjected to ischemia for 3 h by occlusion of the anter ior mesenteric artery with an atraumatic vascular clump. After infusio n of anti-CINC mAbs or isotype-matched mAbs, the intestine was subject ed to reperfusion. The pretreatment with anti-CINC mAbs attenuated isc hemia-reperfusion injury in the small intestine, in association with t he reduction of tumor necrosis factor-alpha and myeloperoxidase produc tion, and resulted in the prolongation of survival. It is concluded th at CINC plays an important role in the onset of rat small intestinal i schemia-reperfusion injury. In addition, blocking the action of CINC, namely, the neutrophil chemotactic activity, may be useful in preventi ng ischemia-reperfusion injury in the small intestine. (C) 1998 Academ ic Press.