Prevention of Small Intestinal Ischemia–Reperfusion Injury in Rat by Anti-cytokine-Induced Neutrophil Chemoattractant Monoclonal Antibody

Abstract

The function of cytokine-induced neutrophil chemoattractant (CINC), which is the rat counterpart to human growth-related gene product belonging to the CXC chemokine subgroup, is based principally on neutrophil-specific chemotactic activity. In addition, we previously reported that plasma CINC was elevated during the period of small intestinal ischemia–reperfusion injury, and that there was a correlation between the degree 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 antibodies (mAbs) reduces small intestinal ischemia–reperfusion injury. Small intestine was subjected to ischemia for 3 h by occlusion of the anterior mesenteric artery with an atraumatic vascular clump. After infusion of anti-CINC mAbs or isotype-matched mAbs, the intestine was subjected to reperfusion. The pretreatment with anti-CINC mAbs attenuated ischemia–reperfusion injury in the small intestine, in association with the reduction of tumor necrosis factor-α and myeloperoxidase production, and resulted in the prolongation of survival. It is concluded that CINC plays an important role in the onset of rat small intestinal ischemia–reperfusion injury. In addition, blocking the action of CINC, namely, the neutrophil chemotactic activity, may be useful in preventing ischemia–reperfusion injury in the small intestine.