Impact of clarithromycin on monocytes-macrophages in patients with coronary arterial disease: a crucial study in cardiovascular research.

BACKGROUND: Besides the known risk factor for coronary artery disease, macrolide antibiotics use has been associated with increased cardiovascular events. This risk is not fully understood, possibly due to macrolide antibiotic effects on macrophage subsets. This study evaluates clarithromycin on macrophage differentiation and polarization in healthy subjects and coronary artery disease patients. METHODS AND RESULTS: Differentiation was induced with GM-CSF or M-CSF with/without clarithromycin. CD14, CD68 and CD163 expression were analyzed. Polarization to M1 or M2 macrophages was induced by IFN-γ and IL-4. In differentiation, clarithromycin decreased CD14 expression in M1 macrophages and reduced M2 markers (CD14. CD163) in healthy controls, but not in coronary artery disease patients. Clarithromycin also induced macrophage apoptosis in healthy subjects. CONCLUSIONS: Clarithromycin appears to differentially modulate macrophage phenotype markers depending on the clinical context. In healthy subjects, it was associated with increased apoptosis in both M1 and M2 macrophages, reduced expression of CD14 and other M1-associated markers, and expression of the CD68 + subset. Additionally, M2-associated markers (CD206 and CD163) were reduced in both healthy subjects and CAD patients. The observed modulation of macrophage markers suggests that clarithromycin influences macrophage polarization pathways. In CAD patients, clarithromycin was associated with decreased expression of M1 markers (CD68 and CD14) and co-stimulatory molecules, consistent with previously described immunomodulatory effects.