HRI shows drug suppresses heart vessel inflammation

In a world-first discovery, scientists at The Heart Research Institute (HRI) and collaborators have shown the anti-inflammatory drug colchicine dramatically reduces local cardiac inflammation when used shortly before cardiac catheterisation.  

Cardiac catheterisation involves threading a catheter (a thin hollow tube) into a major blood vessel in the groin or wrist, which is then advanced up into the heart or coronary vessels.

The study showed that short term colchicine treatment before cardiac catheterisation in acute coronary syndrome (ACS) patients was associated with significantly lower release of inflammatory cytokines.

The study showed that short term colchicine treatment before cardiac catheterisation in acute coronary syndrome (ACS) patients was associated with significantly lower release of inflammatory cytokines.

ACS is characterized by widespread vascular inflammation within the coronary arteries with the potential for the plaque instability or rupture and subsequent heart attack. Acute coronary syndrome (ACS) patients typically exhibit increased local coronary production of inflammatory cytokines, such as interleukin 1b (IL-1b) and interleukin 18 (IL-18).

Excitingly, the study found that just two doses of colchicine before cardiac catheterisation resulted in rapid and significant reductions in the inflammatory cytokines IL-1b, IL-18 and interleukin-6 (IL-6) within the coronary arteries. In addition there was a subsequent reduction in IL-6, a key downstream cytokine strongly associated with inflammation in atherosclerosis.

Dr Sanjay Patel, group leader of the Cell Therapeutics Group at the HRI explains,

“This study examined the key inflammatory cytokines that underpin atherosclerosis. Cytokines are substances that are secreted by immune cells which can act as signals to other cells, and in the case of atherosclerosis they drive inflammation and disease progression. We were surprised by the striking ability of colchicine to suppress the release of these cytokines.”

The study was carried out in collaboration with researchers from Royal Prince Alfred Hospital, the University of Sydney, Catholic University School of Medicine, Santiago, the Paris-Cardiovascular Research Centre and the University of Cambridge.

It looked at 83 patients who underwent a coronary angiogram, in which cardiac catheterisation is performed and dye is used to highlight the coronary arteries during an x-ray. Blood from the coronary sinus, a large vein that directly drains blood from the coronary arteries, was sampled to accurately reflect the coronary artery micro-environment.

Patients were given 1mg of Colchicine, followed by a further 0.5mg one hour later, 24 hours prior to cardiac catheterisation. The results of subsequent sampling of the coronary sinus, aortic root (arterial) and lower right atrium (venous) revealed that colchicine treatment dramatically suppressed IL 1b, IL-18, as well as downstream IL-6.

This is an exciting finding as IL-6 is precursor to C-reactive protein, or CRP, which is significantly associated with the incidence of future cardiovascular events in patients with atherosclerosis. “This study is important because the in vivo (within animals and humans) effects of colchicine on cardiac cytokine release have not been previously studied,” explained Dr Patel.

Colchicine is an inexpensive yet potent anti-inflammatory drug that is currently used to manage acute gout and other inflammatory conditions. 

The mechanisms by which colchicine inhibits the production of inflammatory cytokines are not completely understood. The drug is believed to block the NLRP3 inflammasome, a protein complex within immune cells responsible for the production of active IL-1b and IL-18.

These studies reveal important mechanisms by which colchicine acts to dampen inflammation, primarily through inflammasome inhibition.

“These results are exciting, they are a proof that colchicine is both safe and effective. The next step will be to prove clinical effect through rigorous multicentre clinical trials,” explained Dr Patel. 
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