Colchicine
Colchicine was used for long time as a drug; today it is indicated (in some cases as off-label) in the treatment of gout, Behçet’s disease and for the prevention of pericarditis, Family Mediterranean Fever (FMF), Sweet syndrome, scleroderma, amyloidosis due to FMF uncontrolled.
Probably in these years, the drug obtained the largest clinical success in the treatment of Family Mediterranean Fever (FMF) prophylaxis, on top of traditional use as anti-gout first line treatment. Recently, was also published a very important trial supporting the use of colchicine in secondary prevention post IMA (Acute Myocardial Infarction) and a lot of new papers are available exploring the potential role of colchicine as anti-atherothrombotic inflammatory drug.
The scientific hypothesis of the use of colchicine in SARS-CoV-2 infection is based on the anti-inflammatory properties of the drug.
Recent published data on colchicine seem to suggest a potential synergy in the treatment of cytokine cascade at different levels. In fact, colchicine acts by decreasing inflammation through multiple mechanisms. The principal action mechanism is to bind the tubulin molecule and then inhibit its polymerization as microtubules in neutrophils, with the subsequent inhibition of the migration. In addition, colchicine can alter the distribution of the adhesion molecules on the surface of neutrophils and endothelial cells, leading to a significant inhibition of the interaction between white blood cells and endothelial cells interfering with their transmigration. Considering the above-mentioned facts, there is an increasing evidence that the anti-inflammatory effect of colchicine is multiform. However, the main mechanism of action for CS reduction in patients with SARS-CoV-2 is, probably, the inhibition of IL-1, IL-6 and IL-18 due to the fact that it can interfere with the inflammatory protein complex NLRP3 which plays a central role in the CS.
Colchicine, in addition, inhibits the production of superoxide anion and inhibits the degranulation of mast cells. It is important to note that studies have shown that viroporin E, a component of the SARS associated coronavirus (SARS-CoV), creates Ca2C-permeable ion channels and activates inflammation of NLRP3. In addition, another viroporin 3a induces activation of NLRP3 inflammation. The mechanisms are unclear. Inflammasome NLRP3 can be activated through different mechanisms and it plays an important role in the development of cytokinin storm phase three from SARS-CoV-2. The upstream inhibition of inflammation NLRP3 can be considered as new approach for the prevention or treatment of SARS-CoV-2 infection. Several clinical trials are currently moving to study the efficacy of colchicine in patients with SARS-Cov-2 infection, as detailed in Table 1.