PT  - JOURNAL ARTICLE
AU  - BETTE S. POLLARD
AU  - JORGE C. BLANCOl
AU  - JOHN R. POLLARD
TI  - Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy
AID  - 10.21873/invivo.12221
DP  - 2020 Nov 01
TA  - In Vivo
PG  - 3723--3730
VI  - 34
IP  - 6
4099  - http://iv.iiarjournals.org/content/34/6/3723.short
4100  - http://iv.iiarjournals.org/content/34/6/3723.full
SO  - In Vivo2020 Nov 01; 34
AB  - 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 TNFα-driven NFĸB 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 TNFα, GRO/KC, MIP2, MCP1, and IFNγ, 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.