Colchicine Acutely Suppresses Local Cardiac Production of Inflammatory Cytokines in Patients With an Acute Coronary Syndrome

Gonzalo J Martínez, Stacy Robertson, Jennifer Barraclough, Qiong Xia, Ziad Mallat, Christina Bursill, David S Celermajer, Sanjay Patel, Gonzalo J Martínez, Stacy Robertson, Jennifer Barraclough, Qiong Xia, Ziad Mallat, Christina Bursill, David S Celermajer, Sanjay Patel

Abstract

Background: Interleukin (IL)-1β, IL-18, and downstream IL-6 are key inflammatory cytokines in the pathogenesis of coronary artery disease. Colchicine is believed to block the NLRP3 inflammasome, a cytosolic complex responsible for the production of IL-1β and IL-18. In vivo effects of colchicine on cardiac cytokine release have not been previously studied. This study aimed to (1) assess the local cardiac production of inflammatory cytokines in patients with acute coronary syndromes (ACS), stable coronary artery disease and in controls; and (2) determine whether acute administration of colchicine inhibits their production.

Methods and results: Forty ACS patients, 33 with stable coronary artery disease, and 10 controls, were included. ACS and stable coronary artery disease patients were randomized to oral colchicine treatment (1 mg followed by 0.5 mg 1 hour later) or no colchicine, 6 to 24 hours prior to cardiac catheterization. Blood samples from the coronary sinus, aortic root (arterial), and lower right atrium (venous) were collected and tested for IL-1β, IL-18, and IL-6 using ELISA. In ACS patients, coronary sinus levels of IL-1β, IL-18, and IL-6 were significantly higher than arterial and venous levels (P=0.017, <0.001 and <0.001, respectively). Transcoronary (coronary sinus-arterial) gradients for IL-1β, IL-18, and IL-6 were highest in ACS patients and lowest in controls (P=0.077, 0.033, and 0.014, respectively). Colchicine administration significantly reduced transcoronary gradients of all 3 cytokines in ACS patients by 40% to 88% (P=0.028, 0.032, and 0.032, for IL-1β, IL-18, and IL-6, respectively).

Conclusions: ACS patients exhibit increased local cardiac production of inflammatory cytokines. Short-term colchicine administration rapidly and significantly reduces levels of these cytokines.

Keywords: atherosclerosis; coronary sinus sampling; cytokines; inflammation.

© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.

Figures

Figure 1
Figure 1
Venous, arterial, and coronary sinus (A) IL-1β, (B) IL-18, and (C) IL-6 concentrations in colchicine-naïve ACS and stable CAD patients. Results expressed as mean and SEM. A indicates arterial; ACS, acute coronary syndrome; CAD, coronary artery disease; CS, coronary sinus; IL, interleukin; V, venous.
Figure 2
Figure 2
Transcoronary gradients and venous concentrations of (A) IL-1β, (B) IL-18, and (C) IL-6 according to clinical presentation. Results expressed as mean and SEM. A indicates arterial; ACS, acute coronary syndrome; CS, coronary sinus; IL, interleukin; V, venous.
Figure 3
Figure 3
(A) IL-1β, (B) IL-18, and (C) IL-6 transcoronary gradients in ACS patients and controls, according to colchicine treatment. Results expressed as mean and SEM. ACS indicates acute coronary syndrome; CS-A gradient, coronary sinus–arterial gradient; IL, interleukin.
Figure 4
Figure 4
Effect of short-term colchicine on local cardiac and systemic inflammation in acute coronary syndrome patients. IL indicates interleukin.

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