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The Effect of Low-Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic
Helin Tercan1, Amber van Broekhoven2, Harsh Bahrar1
1Department of Internal Medicine, Radboud University Nijmegen Medical Centre, Nijmegen, The Netherlands.
Insights
Colchicine significantly impacts neutrophil function, reducing recruitment and lowering NGAL levels in patients with coronary artery disease. Its effects on monocyte function are minimal.
Area of Science:
- Cardiovascular Medicine
- Immunology
- Pharmacology
Background:
- Colchicine demonstrates cardiovascular benefits in patients with coronary artery disease.
- The precise mechanisms underlying colchicine's cardioprotective effects remain unclear.
Purpose of the Study:
- To investigate the impact of colchicine on monocyte and neutrophil phenotype and function.
- To elucidate the cellular mechanisms of colchicine in cardiovascular disease.
Main Methods:
- Randomized, double-blind, placebo-controlled, cross-over intervention study.
- Inclusion of patients with a history of myocardial infarction.
- Analysis of neutrophil and monocyte phenotype, function, and RNA expression.
Main Results:
- Colchicine reduced CD62L expression and neutrophil extracellular trap (NET) release, while increasing reactive oxygen species (ROS) production in neutrophils.
- Monocyte effects were limited to decreased HLA-DR expression in specific monocyte subsets.
- Colchicine modulated immunomodulatory gene expression in neutrophils but not monocytes.
Conclusions:
- Colchicine primarily influences neutrophil function, impacting recruitment and inflammatory mediator release.
- The drug's effects on monocyte phenotype and function are less pronounced.
- Findings suggest neutrophil modulation as a key mechanism for colchicine's cardiovascular benefits.
Abstract:
Recent landmark trials showed that colchicine provides a substantial benefit in reducing major cardiovascular events in patients with coronary artery disease. Yet, its exact mechanism of action is still poorly understood. This study aimed to unravel the effect of colchicine on monocyte and neutrophil phenotype and function. A randomized double-blind placebo-controlled cross-over intervention study was executed in patients with a history of myocardial infarction. In neutrophils, colchicine treatment decreased CD62L expression and NGAL release upon ex vivo stimulation and increased PMA-induced ROS production. The effects of colchicine on monocytes were limited to a decrease in HLA-DR expression in the intermediate and nonclassical monocytes. Also, on the level of RNA expression, colchicine did not affect monocyte phenotype, while affecting various immunomodulating genes in neutrophils. Overall, our study suggests that treatment with colchicine affects neutrophil function, particularly by reducing neutrophil recruitment, lowering concentrations of NGAL, and changing the expression of various genes with immunomodulatory potential, whereas the effect on monocytes is limited.
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