Immuno-inflammatory response in patients after myocardial infarction

Abstract

Acute myocardial infarction (AMI) is responsible for an acute inflammatory response followed by a reparative phase resolving after two weeks. Some patients develop adverse ventricular remodeling, supposed to be due to persisting inflammation. To characterize the inflammatory profile of patients after AMI. We prospectively collected blood samples of patients with ST elevation myocardial infarction and coronary revascularization within 12 hours. Plasma and PBMC of patients were collected various times after AMI (H0, H4, H24, H48, D3, M1, M6, M12) and compared to healthy donors. Plasma chemokines concentrations were measured using a multiplex flow cytometry technique. Levels of genes involved in tolerogenicity of dendritic cells and in T cells polarization were evaluated by RT-qPCR. ELISA measured concentrations of cytokines in supernatant of PBMC stimulated with PMA/ionomycin. We observed an early increase of CXCL10, CXCL9, CXCL8, CXCL1, CCL3 and CCL20 compared to healthy donors. The expression level of P2Y11R, HO1, CD39 and STAT3 involved in tolerogenicity increased between H0 and H48, whereas IDO decreased from H0 to M12. We observed an early decrease of CD3, CD8, Tbet and RORγ gene expression and an increase of CD4 from H0 to H48. After stimulation, the PBMC capacity to secrete TNFα, IFNγ, IL1β, IL6 and IL10 decreased after AMI. In the first days after AMI, we observed a secretion of CXCL10, CXCL9; CXCL8, CXCL1; CCL3, CCL20 respectively involved in lymphocytes, neutrophils, and monocytes recruitment. We observed an increase of P2Y11R, HO1, CD39 and STAT3 involved in tolerogenicity of DC and a decrease of IDO; a decrease of CD3, CD8, Tbet and RORγ, and an increase of CD4. We observed an early decrease of PBMC ability to secrete TNFα, IFNγ, IL1β, IL6 and IL10. These observational results suggest that PBMC of patients develop a pro-tolerogenic and anti-inflammatory profile in the first days after AMI.