Inhibiting IL-17 could prove helpful in treating COVID-19

A clinical trial of a drug that targets IL-17 could lead to a preventive treatment for acute respiratory distress syndrome (ARDS) caused by COVID-19.

A research group from the University of Texas MD Anderson Cancer Center makes the case that IL-17 is a plausible but so far overlooked target that could help control ARDS caused by COVID-19.

The work, by Omar Pacha, Mary Alice Sallman and Scott Evans, was published in Nature Reviews Immunology in May 2020.

"IL-17 and IL-17 receptor inhibitors boast an impressive safety history and are widely available," the group wrote.

Why target IL-17? 

Cytokines are a type of small protein active in cell signaling and immune system modulation. The IL-17 cytokine is known to be protective or hyper-inflammatory, depending where it is in the body and what triggers it.

With COVID-19 and related viruses, higher levels of IL-17 correlate with increased severity of disease. IL-17 encourages destruction of the lung during ARDS by producing pro-inflammatory molecules that cause communication to fail in the immune systems feedback system. Additionally, in mice with ARDS excess IL-17 causes lung injury whereas in mice genetically deficient in IL-17 damage to the lung during ARDS is minimal.

An analysis of people who have suffered from ARDS has shown an overrepresentation of IL-17 gene polymorphisms that result in increasing the expression or activity of IL-17. Additionally, those with attenuated IL-17 levels had an increased survival time.

For these reasons, the researchers argue that an IL-17 inhibitor should be considered for reducing inflammation during COVID-19.

The researchers note that there are FDA-approved drugs which currently inhibit IL-17. These drugs are used in psoriasis, psoriatic arthritis and ankylosing spondylitis. With psoriasis, IL-17 contributes to the production of molecules and neutrophils that lead to skin lesions. IL-17 inhibitors decrease the skin inflammation.

In a similar way, researchers suggest, that excessive production of IL-17 found in ARDS could be reduced by IL-17 inhibitors. The researchers cite a study done with mice that showed "improved survival, less lung infiltration and better lung pathology scores" after treatment targeting with IL-17 inhibitors. 

The researchers note that IL-17 could also "serve as both a biomarker of disease severity and a potential target of therapy to mitigate the damage of SARS-CoV-2, particularly to the lung." 

Further, they write, using an IL-17 inhibitor could possibly help mitigate mortality in COVID-19 patients with myocarditis.

There are ongoing clinical trials ongoing investigating inhibitors of IL receptors (IL-1 and IL-6). IL-17 operates "upstream" of both IL-1 and IL-6, thus targeting IL-17 may be highly effective against severe COVID-19.