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

Alexandre Paccalet; Sally Badawi; Bruno Pillot; Lionel Augeul; Laura Mechtouff; Zeina Harhous; Yves Gouriou; Mélanie Paillard; Marine Breuilly; Camille Amaz; Yvonne Varillon; Simon Leboube; Camille Brun; Cyril Prieur; Gilles Rioufol; Nathan Mewton; Michel Ovize; Gabriel Bidaux; Thomas Bochaton; Claire Crola Da Silva

doi:10.1016/j.jacbts.2024.01.019

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

JACC Basic Transl Sci. 2024 Apr 24;9(5):593-604. doi: 10.1016/j.jacbts.2024.01.019. eCollection 2024 May.

Authors

Alexandre Paccalet¹, Sally Badawi¹, Bruno Pillot¹, Lionel Augeul¹, Laura Mechtouff¹, Zeina Harhous¹, Yves Gouriou¹, Mélanie Paillard¹, Marine Breuilly², Camille Amaz³, Yvonne Varillon³, Simon Leboube¹, Camille Brun¹, Cyril Prieur³, Gilles Rioufol³, Nathan Mewton^{1

3

4}, Michel Ovize¹, Gabriel Bidaux¹, Thomas Bochaton^{1

3

5}, Claire Crola Da Silva¹

Affiliations

¹ Laboratoire CarMeN-IRIS Team, INSERM, INRA, Université Claude Bernard Lyon-1, INSA-Lyon, University of Lyon, Bron, France.
² CIQLE, LyMIC, LABEX CORTEX, Université Claude Bernard Lyon 1, Structure Fédérative de Recherche santé Lyon-Est CNRS UAR3453/Inserm US7, Lyon, France.
³ Centre d'Investigation Clinique de Lyon (CIC 1407 Inserm), Hospices Civils de Lyon, Lyon, France.
⁴ Intensive Cardiological Care Division, Louis Pradel Hospital, Hospices Civils de Lyon, Lyon, Bron, France.
⁵ University Claude Bernard Lyon 1, Lyon, France.

Abstract

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.

Keywords: IL-6; MCP-1; STAT3; inflammation; macrophages; myocardial infarction.