Deleterious Anti-Inflammatory Macrophage Recruitment in Early Post-Infarction Phase: Unraveling the IL-6/MCP-1/STAT3 Axis.

Using a translational approach with an ST-segment myocardial infarction (STEMI) cohort and mouse model of myocardial infarction, we highlighted the role of the secreted IL-6 and MCP-1 cytokines and the STAT3 pathway in heart macrophage recruitment and activation. Cardiac myocytes secrete IL-6 and MCP-1 in response to hypoxic stress, leading to a recruitment and/or polarization of anti-inflammatory macrophages via the STAT3 pathway. In our preclinical model of myocardial infarction, neutralization of IL-6 and MCP-1 or STAT3 pathway reduced infarct size. Together, our data demonstrate that anti-inflammatory macrophages can be deleterious in the acute phase of STEMI.

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This work was supported by “Federation Française de Cardiologie,” and LABEX CORTEX (ANR-11-LABX-0042) and FRM (FD202012010540). The authors have reported that they have no relationships relevant to the contents of this paper to disclose.