Exogenous IL-19 attenuates acute ischemic injury and improves survival in male mice with myocardial infarction

Background and purpose: Myocardial infarction (MI) is one of the leading causes of death in China and often results in the development of heart failure. In this work, we tested the therapeutic role of Interleukin-19 (IL-19) in mice with MI and investigated the underlying molecular mechanism. Experimental approach and key results: Protein expression of IL-19 and its receptor in myocardium were upregulated 24 hrs post-MI in male mice. Male mice were injected i.p. with 10ng/g murine recombinant IL-19 immediately after surgery of MI, and it was found that IL-19 treatment decreased infarct and apoptosis in myocardium, accompanied by enhanced heme oxygenase-1 (HO-1) activities and reduced malondialdehyde (MDA) formation. Pretreatment with IL-19 upregulated HO-1 expression in cultured neonatal mouse ventricular myocytes and attenuated oxygen-glucose deprivation (OGD)-induced injuries in vitro. Furthermore, IL-19 preserved cardiac function and improved survival of mice with MI. IL-19 reduced inflammatory infiltrates and suppressed formation of TNF-α, IL-1β, and IL-6. More importantly, IL-19 inhibited polarization toward proinflammatory M1 macrophages and stimulated M2 macrophage polarization in myocardium of mice with MI. IL-19 enhanced protein levels of vascular endothelial growth factor (VEGF) and promoted angiogenesis in myocardium of mice with MI. In addition, IL-19 treatment increased DNA-binding activity of activator of transcription 3 (STAT3) in myocardium of mice with MI. Conclusions and Implications: IL-19 attenuated acute ischemic injury and improved survival of mice with MI, and the mechanisms involved induction of HO-1, M2 macrophage polarization, angiogenesis, and STAT3 activation.