Is colchicine the holy grail for treating inflammation and reducing cardiovascular risk?

Colchicine is extracted from the seeds of colchicum autumnale and is used in herbal medicine. Of note, it is a strong plant alkaloid with toxic effects and is lethal in doses of 1 mg/kg body weight, but in therapeutic doses it has anti-inflammatory, antimicrotubular effects (stopping cell division at the metaphase stage), and it reduces uric acid production. It is anti-inflammatory by inhibiting neutrophil chemotaxis and cytokine release. Colchicine is an inhibitor of the NLPR3 inflammasome and has been shown to reduce pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6), as well as the inflammatory marker C-reactive protein (CRP) in a variety of experimental models and clinical settings [1–3]. [Fig.1.] The drug is used to treat gout attacks, familial Mediterranean fever, and is the drug of choice for pericarditis. Recent years have brought surprisingly positive data on the use of colchicine as an anti-inflammatory substance in coronary artery disease (CAD) and after myocardial infarction (MI), and recently in the treatment of patients with COVID-19 [3].


Invited Commentary
Is colchicine the holy grail for treating inflammation and reducing cardiovascular risk?
Colchicine is extracted from the seeds of colchicum autumnale and is used in herbal medicine. Of note, it is a strong plant alkaloid with toxic effects and is lethal in doses of 1 mg/kg body weight, but in therapeutic doses it has anti-inflammatory, antimicrotubular effects (stopping cell division at the metaphase stage), and it reduces uric acid production. It is anti-inflammatory by inhibiting neutrophil chemotaxis and cytokine release. Colchicine is an inhibitor of the NLPR3 inflammasome and has been shown to reduce pro-inflammatory cytokines including interleukin-1β (IL-1β), interleukin-18 (IL-18) and interleukin-6 (IL-6), as well as the inflammatory marker C-reactive protein (CRP) in a variety of experimental models and clinical settings [1][2][3]. [ Fig.1.] The drug is used to treat gout attacks, familial Mediterranean fever, and is the drug of choice for pericarditis. Recent years have brought surprisingly positive data on the use of colchicine as an anti-inflammatory substance in coronary artery disease (CAD) and after myocardial infarction (MI), and recently in the treatment of patients with COVID-19 [3].

Colchicine in the treatment of COVID-19
In a recent meta-analysis, an attempt was made to summarize knowledge about the impact of colchicine administration on the prognosis of patients with COVID-19. Eight studies were included in the meta-analysis involving 5778 patients. A statistically significant 56% reduction in the risk of severe COVID-19 was demonstrated. Moreover, a statistically significant reduction of 57% in the risk of death in the course of COVID-19 was found [6]. Fig. 1 shows the mechanism of action of colchicine in the setting of SARS-CoV-2 infection.

Summary and important questions for the future
• Should colchicine be incorporated into guidelines on CAD and MI secondary prevention? • What is the role of colchicine in COVID-19 era?
• Are there any more prospective, randomized, double-blinded, placebo controlled clinical trials needed to answer those questions or are we ready to implant this knowledge now?