Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy #MMPMID33144490
Pollard BS; BLANCOl JC; Pollard JR
In Vivo 2020[Nov]; 34 (6): 3723-3730 PMID33144490show ga
BACKGROUND/AIM: Influenza viruses, corona viruses and related pneumotropic viruses cause sickness and death partly by inducing cytokine storm, a hyper-proinflammatory host response by immune cells and cytokines in the host airway. Based on our in vivo experience with digitoxin as an inhibitor of TNFalpha-driven NFkB signaling for cytokine expression in prostate cancer in rats and in cystic fibrosis in humans, we hypothesize that this drug will also block a virally-activated cytokine storm. Materials Methods: Digitoxin was administered intraperitoneally to cotton rats, followed by intranasal infection with 107TCID50/100 g of cotton rat with influenza strain A/Wuhan/H3N2/359/95. Daily digitoxin treatment continued until harvest on day 4 of the experiment. RESULTS: The cardiac glycoside digitoxin significantly and differentially suppressed levels of the cytokines TNFalpha, GRO/KC, MIP2, MCP1, and IFNgamma, in the cotton rat lung in the presence of influenza virus. CONCLUSION: Since cytokine storm is a host response, we suggest that digitoxin may have a therapeutic potential not only for influenza and but also for coronavirus infections.
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In+Vivo 2020 ; 34 (6): 3723-3730
