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PROHLÍŽENÍ ABSTRAKTA

IN VITRO ASSESSMENT OF ANTI-INFLAMMATORY AND CYTOTOXICITY PROPERTIES OF COLCHICINE
Tématický okruh: okruh
Typ: Ústní sdělení - lékařské , Číslo v programu: 45
Malý M.1, Viktorová J.2, Strnad O.2, Ruml T.2, Stránská M.3

1 Interní klinika - Kardiologické oddělení, Ústřední Vojenská Nemocnice - Vojenská Fakultní Nemocnice, Praha, 2 Ústav biochemie a mikrobiologie, Vysoká škola chemicko-technologická, Praha, 3 Ústav analýzy potravin a výživy, Vysoká škola chemicko-technologická, Praha


Inflammation plays a substantial role in the process of atherosclerosis. The key players are monocytes transformed to macrophages and coronary artery endothelial cells. Limited anti-inflammatory drugs are currently available – antibodies for IL-1 (CANTOS) and colchicine (COLCOT, LoDoCo-2 trial). Here, we describe the molecular mechanism of colchicine downregulation of inflammation processes in connection to its cytotoxic effects on treated cells.
Human coronary artery endothelial cells (HCAEC) were polarized toward M1 pro-inflammatory phenotype responsible for production of IL-6.  The production of IL-6 was negated by addition of colchicine in dose-dependent manner. 13.4 ± 0.8 mg/L of colchicine decreased the production of IL-6 by 50% in HCAEC cells.
Similarly, human monocytic cell line THP-1 was differentiated into macrophages by incubation in the presence of phorbol-12-myristate-13-acetate, which leads to a macrophage-like phenotype characterized by changes in morphology and adhesion. In concentrations higher than 7.5 mg/L, colchicine significantly increased the production of TNFα and IL-6 indicating induction of stress conditions and production of inflammatory markers by macrophages.
Colchicine did not show direct cytotoxicity against HCAEC or THP-1 (24h treatment) even at the highest tested concentration of 100 mg/L, but induced the expression of nephrotoxic markers in human renal tubular epithelial kidney cells.
In summary, our in vitro results show the potential of colchicine to reduce inflammation in coronary artery endothelial cells, but at the same dose, colchicine induces stress conditions and an inflammatory environment in monocytes. At the same time, it is necessary to draw attention to the nephrotoxic effects of colchicine.