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 recent review article published in the journal
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
Existing drugs that partly inhibit HMGB1
'The collated science shows that HMGB1 probably plays a pivotal part in the development of acute lung damage, regardless of cause,' says
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.
'In publishing our review paper, we hope to give guidance on existing drugs with the potential to mitigate HMGB1-mediated damage,' says
Several other interesting findings
Specific HMGB1 inhibitors have shown promise in two decades of repeated animal studies and there are already fully developed humanised antibodies targeting HMGB1. But it is not known whether the treatment works in humans and if so, whether the adverse effects would be acceptable.
'To test this hypothesis would require sums that are difficult for academic researchers to get their hands on,' he says.
There are several other findings that make HMGB1 particularly interesting to study for severe pulmonary inflammation, according to
'There are also studies showing that arterial blood only contains 60 percent of the HMGB1 in venous blood,' he continues, 'meaning that a substantial amount of HMGB1 is retained in lung circulation.'
The research was financed by the
Publication
'Extracellular HMGB1: A therapeutic target in severe pulmonary inflammation including COVID-19?'.
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