Hypothesis: Pentoxifylline is a potential cytokine modulator therapeutic in COVID-19 patients

Pharmacol Res Perspect. 2020 Aug;8(4):e00631. doi: 10.1002/prp2.631.

Abstract

We propose a new hypothesis that the established drug pentoxifylline deserves attention as a potential repurposed therapeutic for COVID-19. Pentoxifylline is an immunomodulator with anti-inflammatory properties. It is a nonselective phosphodiesterase inhibitor and through Adenosine A2A Receptor-mediated pathways reduces tumor necrosis factor alpha, interleukin 1, interleukin 6, and interferon gamma and may act to reduce tissue damage during the cytokine storm host response to SARS-CoV-2 infection. This agent has been used clinically for many years and has a favorable profile of safety and tolerability. Pre-clinical data support pentoxifylline as effective in cytokine-driven lung damage. Clinical studies of pentoxifylline in radiation and cytokine-induced lung damage in humans are positive and consistent with anti-inflammatory efficacy. Pentoxifylline is a readily available, off-patent and inexpensive drug, suitable for large-scale use including in resource-limited countries. Current trials of therapeutics are largely focused on the inhibition of viral processes. We advocate urgent randomized trials of pentoxifylline for COVID-19 as a complementary approach to target the host responses.

Keywords: COVID-19; SARS-CoV-2; cytokine; immunomodulation; pentoxifylline; pneumonia; viral.

Publication types

  • Review

MeSH terms

  • Betacoronavirus*
  • Coronavirus Infections / drug therapy*
  • Humans
  • Pandemics
  • Pentoxifylline / pharmacology
  • Pentoxifylline / therapeutic use*
  • Phosphodiesterase Inhibitors / therapeutic use*
  • Pneumonia, Viral / drug therapy*
  • Research Design
  • Tumor Necrosis Factor-alpha / blood
  • Tumor Necrosis Factor-alpha / physiology

Substances

  • Phosphodiesterase Inhibitors
  • Tumor Necrosis Factor-alpha
  • Pentoxifylline

Supplementary concepts

  • COVID-19
  • COVID-19 drug treatment
  • severe acute respiratory syndrome coronavirus 2