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.