Recombinant human interleukin-1 receptor antagonist treatment protects rats from myocardial ischemia-reperfusion injury.

The interleukin-1 (IL-1) signaling pathway plays a vital role in multiple mechanisms associated with myocardial ischemia-reperfusion (I/R) injury, including inflammation and apoptosis. An IL-1 receptor antagonist (IL-1Ra) can block IL-1 by competitive binding to the IL-1 receptor type I (IL-1RI) and thus may provide a cardioprotective effect. In the present investigation, we determined whether exogenous administration of recombinant human IL-1Ra (rhIL-1Ra) provides a protective role against myocardial I/R injury. Sprague-Dawley rats underwent surgical coronary artery ligation (or sham operation) by occlusion of the left anterior descending artery (LAD) for 30 min followed by reperfusion. After 30 min of reperfusion, a 2 mg/kg dose of rhIL-1Ra was injected subcutaneously. This was followed up with once daily injections for seven days. Echocardiography revealed that ejection fraction (EF) values were significantly greater in the rhIL-1Ra-treated animals. RhIL-1Ra was found to reduce the severity of myocardial injury and increase the viability of the cardiac tissue. There was found to be less IL-1β expression in rhIL-1Ra-treated animals than in controls. These results provide compelling data to suggest administration of IL-1Ra could have a significant cardioprotective effect against myocardial I/R injury and thus IL-1Ra could emerge as a potential clinical drug for the treatment of myocardial I/R injury.