Colchicine as a Novel Therapy for Suppressing Chemokine Production in Patients With an Acute Coronary Syndrome: A Pilot Study

Clin Ther. 2019 Oct;41(10):2172-2181. doi: 10.1016/j.clinthera.2019.07.015. Epub 2019 Aug 10.

Abstract

Purpose: Existing literature reports that colchicine inhibits inflammasome activation and downstream inflammatory cytokine production and stabilizes coronary plaque. However, colchicine's effect on chemokines, which orchestrate multiple atheroinflammatory pathways, is unknown.

Methods: Patients with acute coronary syndrome (ACS) were randomly assigned to colchicine (1.5 mg PO) (n = 12; mean age, 65.2 years) or no treatment (n = 13; mean age, 62.2 years). Blood samples were collected during cardiac catheterization within 24 hours of colchicine administration from the coronary sinus, aortic root, and right atrium. Patients with colchicine-naive stable angina (SAP) (n = 13; mean age, 66.8 years) were additionally sampled. Serum chemokine levels were analyzed with ELISA. In parallel, monocytes from healthy donors were isolated and subjected to colchicine treatment.

Findings: Transcoronary (TC) levels of chemokine ligand 2 (CCL2) and C-X3-C motif chemokine ligand 1 (CX3CL1) were significantly elevated in patients with ACS versus patients with SAP (P < 0.01). TC chemokine ligand 5 (CCL5) levels were not significantly (P = 0.084) elevated in patients with ACS versus patients with SAP. Colchicine treatment markedly reduced TC levels of CCL2, CCL5, and CX3CL1 in patients with ACS (P < 0.05). In vitro colchicine suppressed CCL2 gene expression in stimulated monocytes (P < 0.05). Colchicine treatment reduced the intracellular concentration of all 3 chemokines (P < 0.01) and impaired monocyte chemotaxis (P < 0.05).

Implications: Here, we report for the first time that short-term colchicine therapy significantly reduces the local production of coronary chemokines, in part by attenuating production of these mediators by monocytes. These data provide further evidence of colchicine's beneficial role in patients with ACS.

Keywords: Acute coronary syndrome; Atherosclerosis; Coronary heart disease; Inflammation; Therapeutics.

Publication types

  • Randomized Controlled Trial
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Coronary Syndrome / blood
  • Acute Coronary Syndrome / drug therapy*
  • Aged
  • Chemokine CX3CL1 / metabolism
  • Chemokines / metabolism*
  • Colchicine / pharmacology*
  • Female
  • Humans
  • Male
  • Middle Aged
  • Monocytes / metabolism
  • Pilot Projects

Substances

  • CX3CL1 protein, human
  • Chemokine CX3CL1
  • Chemokines
  • Colchicine