Background:
COVID-19, caused by SARS-CoV-2, is a potentially lethal, rapidly-expanding pandemic
and many efforts are being carried out worldwide to understand and control the disease. COVID-19 patients may
display a cytokine release syndrome, which causes severe lung inflammation, leading, in many instances, to
death.
Objective:
This paper is intended to explore the possibilities of controlling the COVID-19-associated hyperinflammation
by using licensed drugs with anti-inflammatory effects.
Hypothesis:
We have previously described that pentoxifylline alone, or in combination with oxypurinol, reduces
the systemic inflammation caused by experimentally-induced pancreatitis in rats. Pentoxifylline is an inhibitor of
TNF-α production and oxypurinol inhibits xanthine oxidase. TNF-α, in turn, activates other inflammatory genes
such as Nos2, Icam or IL-6, which regulate migration and infiltration of neutrophils into the pulmonary interstitial
tissue, causing injury to the lung parenchyma. In acute pancreatitis, the anti-inflammatory action of pentoxifylline
seems to be mediated by the prevention of the rapid and presumably transient loss of PP2A activity. This may
also occur in the hyperinflammatory -cytokine releasing phase- of SARS-CoV-2 infection. Therefore, it may be
hypothesized that early treatment of COVID-19 patients with pentoxifylline, alone or in combination with oxypurinol,
would prevent the potentially lethal acute respiratory distress syndrome.
Conclusion:
Pentoxifylline and oxypurinol are licensed drugs used for diseases other than COVID-19 and, therefore,
phase I clinical trials would not be necessary for the administration to SARS-CoV-2- infected people. It
would be worth investigating their potential effects against the hyperinflammatory response to SARS-CoV-2
infection.
Strain-and Age-associated Changes in Cytokine Release from Endotoxin-treated Mouse Monocytes