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

Hendry, Bruce M.; Stafford, Nina; Arnold, Ahran D.; Sangwaiya, Arvind; Manglam, Vijay; Rosen, Stuart D.; Arnold, Jayantha

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.