The Effect of Low‐Dose Colchicine on the Phenotype and Function of Neutrophils and Monocytes in Patients with Chronic Coronary Artery Disease: A Double‐Blind Randomized Placebo‐Controlled Cross‐Over Study

Author:

Tercan Helin1ORCID,van Broekhoven Amber2ORCID,Bahrar Harsh1,Opstal Tjerk23,Cossins Benjamin C.1,Rother Nils4ORCID,Rodwell Laura5,Bekkering Siroon1ORCID,El Messaoudi Saloua2,Riksen Niels P.1ORCID,Cornel Jan H.236ORCID

Affiliation:

1. Department of Internal Medicine Radboud University Nijmegen Medical Centre Nijmegen The Netherlands

2. Department of Cardiology Radboud University Medical Centre Nijmegen The Netherlands

3. Department of Cardiology Northwest Clinics Alkmaar The Netherlands

4. Department of Nephrology Radboud University Medical Centre Nijmegen The Netherlands

5. Section Biostatistics, IQ Health Radboud University Medical Center Nijmegen The Netherlands

6. Dutch Network for Cardiovascular Research (WCN) Utrecht The Netherlands

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.

Publisher

Wiley

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