In severe cases of COVID-19, a massive release of the endogenous protein HMGB1 in the lungs may contribute to pulmonary inflammation and tissue damage, according to a review article published today in the scientific journal Molecular Medicine . The researchers conclude that the inflammation could hypothetically be treated with an HMGB1 inhibitor.
Severe viral infections can cause the immune system to over-respond to the intruding infectious agents and to produce large amounts of proteins called cytokines in what is called a cytokine storm. This can, in turn, give rise to serious, possibly fatal inflammation and tissue damage.
One of the molecules responsible for cytokine storms is the proinflammatory protein HMGB1. The new review paper describes the molecular mechanisms behind HMGB1-mediated inflammation, including the pulmonary inflammation that can develop in severe cases of COVID-19.
The article is partly based on 20 years' research on HMGB1 that Ulf Andersson's research group at Karolinska Institutet in Sweden has conducted with Kevin Tracey's group at the Feinstein Medical Research Institute in New York, USA.
The collated science shows that HMGB1 probably plays a pivotal part in the development of acute lung damage, regardless of cause. It would therefore be interesting to test whether specific HMGB1 inhibitors would be able to reduce inflammation and the subsequent lung damage caused by the new coronavirus." Ulf Andersson, Senior Professor, Department of Women's and Children's Health, Karolinska Institute
While there are currently no specific HMGB1 inhibitors tested on humans, there are a number of existing drugs that are approved for other biological effects and that also partly inhibit HMGB1. However, they have not yet been tested for the purpose of reducing inflammation. Related Stories
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