The systemic deletion of interleukin-1 alpha reduces myocardial inflammation and attenuates ventricular remodeling in murine myocardial infarction

Myocardial inflammation following myocardial infarction (MI) is crucial for proper myocardial healing, yet, dysregulated inflammation may promote adverse ventricular remodeling and heart failure. IL-1 signaling contributes to these processes, as shown by dampened inflammation by inhibition of IL-1 beta or the IL-1 receptor. In contrast, the potential role of IL-1 alpha in these mechanisms has received much less attention. Previously described as a myocardial-derived alarmin, IL-1 alpha may also act as a systemically released inflammatory cytokine. We therefore investigated the effect of IL-1 alpha deficiency on post-MI inflammation and ventricular remodeling in a murine model of permanent coronary occlusion. In the first week post-MI, global IL-1 alpha deficiency (IL-1 alpha KO mice) led to decreased myocardial expression of IL-6, MCP-1, VCAM-1, hypertrophic and pro-fibrotic genes, and reduced infiltration with inflammatory monocytes. These early changes were associated with an attenuation of delayed left ventricle (LV) remodeling and systolic dysfunction after extensive MI. In contrast to systemic Il1a-KO, conditional cardiomyocyte deletion of Il1a (CmIl1a-KO) did not reduce delayed LV remodeling and systolic dysfunction. In conclusion, systemic Il1a-KO, but not Cml1a-KO, protects against adverse cardiac remodeling after MI due to permanent coronary occlusion. Hence, anti-IL-1 alpha therapies could be useful to attenuate the detrimental consequences of post-MI myocardial inflammation.