Inhibition of interleukin-8 blocks myocardial ischemia-reperfusion injury.
BACKGROUND
Interleukin-8 is thought to play a role in neutrophil activation and transcapillary migration into 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 rabbit interleukin-8 (ARIL8.2) would attenuate the degree of myocardial injury encountered during reperfusion.


METHODS
In New Zealand White rabbits, the large branch of the marginal coronary artery supplying most of the left ventricle was occluded for 45 minutes, followed by 2 hours of reperfusion. Fifteen minutes before reperfusion, animals were given an intravenous bolus of either 2 mg/kg of ARIL8.2 or 2 mg/kg anti-glycoprotein-120, an isotype control antibody that does not recognize interleukin-8. At the completion of the 120-minute reperfusion period, infarct size was determined.


RESULTS
In the area at risk for infarction, 44.3% +/- 4% of the myocardium was infarcted in the anti-glycoprotein-120 group compared with 24.8% +/- 9% in the ARIL8.2 group (p < 0.005). In control animals, edema and diffuse infiltration of neutrophils were observed predominantly in the infarct zone and the surrounding area at risk. Tissue myeloperoxidase determinations did not differ significantly between groups, indicating that the cardioprotective effect of ARIL8.2 was independent of an effect on neutrophil infiltration.


CONCLUSIONS
A specific monoclonal antibody that neutralizes interleukin-8 significantly reduces the degree of necrosis in a rabbit model of myocardial ischemia-reperfusion injury.
Department of Surgery, University of Washington, Seattle 98195, USA.
E M
EM
Boyle
J C
JC
Kovacich
C A
CA
Hèbert
T G
TG
Canty
E
E
Chi
E N
EN
Morgan
T H
TH
Pohlman
E D
ED
Verrier
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D004195:Disease Models, Animal; D016209:Interleukin-8 / Q000037:antagonists & inhibitors* / Q000097:blood / Q000276:immunology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018375:Neutrophil Activation / Q000187:drug effects / Q000502:physiology; D009504:Neutrophils / Q000502:physiology; D009195:Peroxidase / Q000378:metabolism; D011817:Rabbits; D012039:Regional Blood Flow / Q000187:drug effects
D000911:Antibodies, Monoclonal; D016209:Interleukin-8; D009195:Peroxidase