Introduction: The benefits of vessel recanalization in acute myocardial infarction (AMI) are limited by ischemia/reperfusion (IR) injury. We have reported IL-11, a kind of IL-6 family cytokine, confers resistance to IR injury on cardiomyocytes both in vitro and in vivo and reduces infarct size and improved ventricular function after I/R injury in vivo. Importantly, recombinant human IL-11 (rhIL-11) was clinically used for the prevention of severe thrombocytopenia after chemotherapy under the approval of FDA.
Hypothesis: The aim of this study was to evaluate the safety and feasibility of rhIL-11, adjunct to primary percutaneous coronary intervention (PCI) in AMI.
Methods: Four patients with STEMI undergoing primary PCI were enrolled based on inclusion criteria, such as culprit lesion of #6 or #7 with TIMI flow grade 0 or 1 on coronary angiography (CAG). Just after diagnosis by CAG, rhIL-11 (6 or 25 μg/kg) was intravenously administered for a period of 3 hours (hr). The primary endpoint were safety and tolerability for 7days after the administration. Serum creatine kinase (CK) was measured pre- and 1, 2.5, 3, 6, 10, 15, 24, 48 hr after injection. Echocardiography was performed pre-, 7days, 3 and 6 months after injection.
Results: Just after injection of rhIL-11, PCI was successfully performed and no severe or serious drug adverse events occurred through the observation period in any cases. And they left the hospital without symptoms of heart failure. In addition, no unexpected reduction in left ventricular ejection fraction (LVEF) was observed in the patients treated with rhIL-11 (LVEF, 39.8±8.8 %; CKmax, 6906.3±3546 U/L), compared with non-treated internal controls with similar baseline demographics including CKmax and LVEF at chronic phase after AMI.
Conclusions: Conclusively, we described the four cases of rhIL-11 therapy against STEMI as a novel cytokine therapy for the first time, and this therapy was feasible and well tolerated in AMI. In order to address the efficacy of rhIL-11 therapy, we have been preparing randomized controlled trial to investigate efficacy and safety of rhIL-11 in the patients with STEMI, and the protocol for the trial was approved as advanced medical care by Japanese Ministry of Health, Labour and Welfare last December.