Pentoxifylline and Oxypurinol: Potential Drugs to Prevent the "Cytokine Release (Storm) Syndrome" Caused by SARS-CoV-2?

Curr Pharm Des. 2020;26(35):4515-4521. doi: 10.2174/1381612826666200811180232.


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.

Keywords: COVID-19; Pentoxifylline; SARS-CoV-2; cytokine release syndrome; oxypurinol; pro-inflammatory cytokines; serine/ threonine phosphatase PP2A; systemic inflammatory response.

MeSH terms

  • Acute Disease
  • Animals
  • Betacoronavirus
  • COVID-19
  • Coronavirus Infections / drug therapy*
  • Cytokine Release Syndrome / prevention & control*
  • Cytokine Release Syndrome / virology
  • Humans
  • Oxypurinol / therapeutic use*
  • Pancreatitis
  • Pandemics
  • Pentoxifylline / therapeutic use*
  • Pneumonia, Viral / drug therapy*
  • Rats
  • SARS-CoV-2


  • Oxypurinol
  • Pentoxifylline