The Sooner, the Better: Anti-inflammation in Acutemyocardial Infarction

Thomas F. Lüscher


Eur Heart J. 2020;41(42):4100-4102. 

In This Article

Learning From Gout

What might be the mechanism of action of colchicine which traditionally is used in the management of gout? The mechanisms of action of colchicine are obviously multiple and not completely understood.[22] First of all, colchicine binds to free tubulin, an αβ heterodimer initially identified as the cellular colchicine-binding protein that forms microtubules upon polymerization and interacts with many regulatory cellular proteins (Figure 1). Thereby colchicine inhibits cell migration and cytokine release, particularly by white blood cells. Colchicine also modulates superoxide production by leucocytes[23] which is in part responsible for the inhibition of neutrophil adhesion, extravasation, and recruitment by altering neutrophil L-selectin expression and endothelial cell E-selectin distribution, and suppressing the release of the chemotactic leukotriene B4. Whether all of these effects are secondary to the impact of colchicine on microtubules remains to be determined. Importantly, however, colchicine inhibits the Nod-Like Receptor Protein 3 (NLRP3) inflammasome (while urate crystals activate i)t,[24] thereby suppressing caspase-1 activation and the subsequent release of IL-1β and IL-18; Figure 1). As the NLRP3 inflammasome is expressed in the myeloid lineage,[25] colchicine appears to mainly interfere with neutrophils and monocytes and macrophages, i.e. the innate immune system that is involved in ACS, rather than the adaptive immune system.

Figure 1.

Molecular effects of colchicine in white blood cells via tubulin and microtubuli as well asNod-Like Receptor Protein 3 (NLRP3) inflammasome. Inset left, urate crystals; inset right, cholesterol crystals (modified from ImazioM, Gaita F. Heart April 2016 Vol 102No 8).