Blood sugar-lowering drug Metformin can prevent pulmonary or lung inflammation, a major factor in Covid-19 severity and mortality, researchers have found in studies of mice infected by the SARS-CoV-2 coronavirus.
Metformin is often used as an early therapy for Type-2 diabetes. It works by lowering glucose production in the liver, reducing blood sugar levels that, in turn, improve the body's response to insulin. But scientists have also noted that metformin possesses anti-inflammatory properties, though the basis for this activity was not known.
A multi-institution team led by researchers at University of California San Diego identified the molecular mechanism for the anti-inflammatory activity of metformin.
The researchers focussed on a mouse model of acute respiratory distress syndrome (ARDS), a life-threatening condition in which fluids leak into the lungs, making breathing difficult and restricting oxygen supply to essential organs.
ARDS is triggered by trauma and by bacterial or viral infections. It is a frequent cause of death in patients hospitalised with Covid-19.
The findings published online in the journal Immunity showed that metformin administered to mice prior to or after exposure to bacterial endotoxin, a surrogate for bacterial pneumonia, resulted in the inhibition of ARDS onset and lessening of its symptoms. Metformin also produced a marked reduction in mortality in endotoxin-challenged mice and inhibited IL-1beta production and inflammasome assembly within alveolar macrophages -- immune cells found in the lungs.
IL-1beta, along with IL-6, are small proteins called cytokines that cause inflammation as an early immune response. Their amounts are often highly elevated in persons infected by SARS-CoV-2, creating "cytokine storms" in which the body starts attacking its own cells and tissues. They are signs of an acute immune response gone awry.
Production of IL-1beta depends on a large protein complex called the inflammasome, whose presence in lung tissue is found to be highly increased in deceased Covid-19 patients, researchers said.
The authors said the findings suggest metformin may have therapeutic potential for treating a variety of neurodegenerative and cardiovascular diseases in which inflammasome activation is a factor.
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