INHIBITION OF INTERLEUKIN-8 BLOCKS MYOCARDIAL ISCHEMIA-REPERFUSION INJURY

Introduction: Interleukin-8 is thought to play a role in neutrophil ac tivation and transcapillary migration irate the interstitium. Because neutrophils are principal effector cells in acute myocardial ischemia- reperfusion injury, we postulated that the inhibition of interleukin-8 activity with a neutralizing monoclonal antibody directed against rab bit interleukin-8 (ARIL8.2) would attenuate the degree of myocardial i njury encountered during reperfusion. Methods: In New Zealand White ra bbits, the large branch of the marginal coronary artery supplying most of the left ventricle was occluded for 45 minutes, followed by 2 hour s of reperfusion. Fifteen minutes before reperfusion, animals were giv en an intravenous bolus of either 2 mg/kg of ARIL8.2 or 2 mg/kg anti-g lycoprotein-120, an isotype control antibody that does not recognize i nterleukin-8. Al the completion of the 120-minute reperfusion period, infarct size was determined, Results: In the area at risk for infarcti on, 44.3% +/- 4% of the myocardium was infarcted in the anti-glycoprot ein-120 group compared with 24.8% +/- 9% in the ARIL8.2 group (p < 0.0 05). In control animals, edema and diffuse infiltration of neutrophils were observed predominantly in the infarct zone and the surrounding a rea at risk, Tissue myeloperoxidase determinations did not differ sign ificantly between groups, indicating that the cardioprotective effect of ARIL8.2 was independent of an effect on neutrophil infiltration. Co nclusions: A specific monoclonal antibody that neutralizes interleukin -8 significantly reduces the degree of necrosis in a rabbit model of m yocardial ischemia-reperfusion injury.