Researchers have come across a possible new therapeutic approach for severe courses.

© HANS PUNZ

Berlin, Linz – Researchers from Germany and Austria have taken a closer look at a mechanism by which cells react to stress. This so-called “senescence” plays her work in the trade journal Nature According to it, it also plays an important role in the dreaded extreme inflammatory reaction (cytokine storm) in severe Covid 19 diseases. With active ingredients that target such senescent cells, the impending derailment could perhaps be counteracted at an early stage in the future.

At the end of a severe Covid-19 course, there is often an excessive reaction of the immune system. In the process, high concentrations of certain proteins (cytokines) are formed, which cause a massive inflammatory reaction throughout the body. The scientists from the Berlin Charité, from the Max Delbrück Center for Molecular Medicine in the German Helmholtz Association (MDC), the University of Linz (JKU) and the Linz University Hospital have now shown that senescence is involved.

Protection program of cells from stress

This is actually a protection program for cells against stress and impending damage. Senescent cells are programmed to stop dividing in order not to pass on their damage to the next generation of cells. This protects the body from cancer, for example, according to a broadcast from the Charité on Monday. Such cells continue to produce messenger substances that drive inflammation, which is important for wound healing, for example. This type of cell aging with the associated excessive excretion of inflammatory substances also plays a role in the development of age-related diseases such as diabetes or vascular calcification.

However, infections with viruses can also trigger senescence. This is also the case of the investigation by the team around Clemens Schmitt, who works at the Charité and the Kepler Clinic in Linz, in the case of infections with the SARS-CoV-2 virus. Studies on infected cell cultures and animals have shown that the virus triggers senescence in mucosal cells in the upper respiratory tract. The inflammatory messenger substances secreted there in turn attract representatives of the immune system – the phagocytes or macrophages. They actually come to turn off the senescent cells in the mucous membranes. However, they are also put into this state by the messenger substances.

As a result, the macrophages can get into the lungs, where they further secrete inflammatory substances. In this way, they can also drive cells there, such as those that line the pulmonary blood vessels, into senescence. The researchers describe the complex process that can then form clumps in the blood vessels that damage the lung function.

Possible new point of attack in Covid-19 therapy

This is apparently a “very important driver of an inflammatory storm that significantly causes a large number of characteristic features of Covid-19 pneumonia, such as vascular damage or microthrombosis,” says the first author of the work, Soyoung Lee. Conversely, an early attack on cells that have been modified in this way could be a new point of attack in the treatment of severe Covid 19 infections.

In hamsters and mice, four known active ingredients, in various combinations or on their own, turned out to be a way of containing the inflammatory storm and lessening the damage to the lungs. One of these so-called senolytics is also very promising for use in humans. For Schmitt, the new results are “very encouraging”. However, the senolytics also have side effects. In order to use the active ingredients, “further clinical studies are necessary, some of which various institutions around the world have already set up,” says Schmitt. (WHAT)

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