Journal
IN VIVO
Volume 34, Issue 6, Pages 3723-3730Publisher
INT INST ANTICANCER RESEARCH
DOI: 10.21873/invivo.12221
Keywords
Virus; influenza; coronavirus; SARS; COVID-19; RNA-virus; cardiac glycosides; digitoxin; digoxin; ouabain; oleandrin; inflammation; cytokine storm; TNF alpha; GRO/KC; MIP-2; MCP1; IFN gamma
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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 TNF alpha-driven NF kappa B 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 TNF alpha, GRO/KC, MIP2, MCP1, and IFN gamma, 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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