25 December 2017

New properties of old drugs

A group of anti-inflammatory drugs approved for the treatment of rheumatoid arthritis helps to "clean" infected cells from the immunodeficiency virus.

When culturing cells obtained from the blood of HIV-infected people, a group of researchers from the Case Western Reserve University School of Medicine, Ohio, discovered the ability of anti-inflammatory drugs from the group of Jak inhibitors (tofacitinib, ruxolitinib) to block the exit of HIV from infected cells, preventing its spread, as well as the breakdown of the viral reservoir.

The viral reservoir is a small group of immune cells in whose genome the virus has embedded itself, and is one of the serious obstacles to the treatment of viral infection. These cells are not recognized by the body's immune system, since the virus inside is in a dormant state. But as soon as the concentration of the antiviral drug in the blood decreases, the virus is activated and leaves the cell.

The study proved that anti-inflammatory drugs of the Jak-inhibitor group help to solve this problem.

 37 HIV-infected patients who had been receiving antiretroviral therapy for a long time donated blood samples. The size of the viral reservoir was determined in them – the Jak enzyme was active in cells infected with HIV. The introduction of an agent blocking this enzyme caused the destruction of infected cells. Laboratory studies have confirmed that Jak inhibitors prevent the spread of the virus into healthy cells.

There are pro-inflammatory cytokines that are produced during inflammatory processes, including autoimmune diseases and, in particular, rheumatoid arthritis. Jak inhibitors block pro-inflammatory cytokines and stop inflammation.

In an earlier study, the authors proved the effectiveness of the Jak inhibitor ruxolitinib in mouse models with HIV-associated encephalitis.

The totality of the data obtained proves the effectiveness of Jak inhibitors for the treatment of HIV infection not only in the vascular bed, but also in the central nervous system, where it can hide.

The advantage of Jak inhibitors is their lack of systemic immune suppressive activity, rather the opposite - they modulate immunity. In other words, they do not affect the function of the body's immune system and do not interfere with immune cells fighting infection.

Suppression of the activity of the Jak enzyme in HIV-infected cells reduces the production of pro-inflammatory cytokines and prevents the spread of the virus, since it requires inflammatory activity in the cell for replication. In addition, Jak inhibitors reduce the lifespan of the reservoir cell by affecting the Bcl-2 protein.

Jak inhibitors have a selective effect - their activity is directed only at infected cells and does not affect healthy ones in any way.

The data obtained substantiate the need to study the efficacy and safety of ruxolitinib among patients with HIV infection. In addition, these studies will allow to evaluate the long-term results of treatment.

Article by Christina Gavegnano et al. Novel mechanisms to inhibit HIV reservoir seeding using Jak inhibitors is published in the journal PLOS Pathogens.

Aminat Adzhieva, portal "Eternal Youth" http://vechnayamolodost.ru based on the materials of CWRUMed: Selective Suppression of Inflammation Could Deplete HIV and Control HIV Activation.

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