We investigated the cardioprotective effects of rat interleukin-10 in a murine model of myocardial ischemia-reperfusion (20 min ischemia, 24 h reperfusion). Interleukin-10 (100 microg/rat) administered 15 min prior to reperfusion, significantly (P < 0.01) attenuated myocardial injury compared to rats receiving only 0.9% saline as a vehicle, as indicated by a reduced loss of myocardial creatine kinase from the ischemic-reperfused myocardium. Cardiac myeloperoxidase activity was also significantly (P < 0.01) attenuated by interleukin-10 within the ischemic-reperfused region compared to vehicle treated rats. To further investigate the mechanism of interleukin-10 we observed the in vitro adherence of neutrophil to rat vascular endothelium. Interleukin-10 treatment significantly (P < 0.05) attenuated neutrophil adherence to rat superior mesenteric artery endothelium stimulated with interleukin-1beta. Thus, interleukin-10 demonstrated significant cardioprotective effects as evidenced by a decrease in myocardial creatine kinase loss as well as an inhibition of neutrophil accumulation within the myocardium. It appears as though interleukin-10 mediates its effects, at least in part, by inhibiting leukocyte-endothelial interactions.