Mechanism of the anti-inflammatory effect exerted by colchicine on pro-inflammatory macrophages and neutrophils

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Although colchicine serves as a first-line treatment of gout and familial Mediterranean fever (1), previous clinical trials such as COLTOT and LoDoCo showed that colchicine treatment significantly reduces risk of cardiovascular events in coronary heart disease patients (2, 3). However, the understanding to the mechanisms inducing cardiovascular disease (CVD) protective properties is yet to be fully covered.In this project, we will map on the anti-inflammatory properties exerted by growth differentiation factor 15 (GDF15), a hepatokine secreted post-colchicine treatment. In murine myeloid cells, GDF15 was previously shown to suppress IL-1beta production, important pro-inflammatory cytokine, and cell adhesion and recruitment. (4, 5). We will expand on these findings by further investigation of the GDF15 and FGF1, potential binding partner, effects on cytokine production, marker expression, metabolic profile and phagocytosis in pro-inflammatory macrophages and neutrophils as they are major contributors to progression of CVD, type II diabetes or autoimmune diseases.