Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy
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 si...
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| Veröffentlicht in: | In vivo (Athens) 2020-11, Vol.34 (6), p.3723-3730 |
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| creator | Pollard, Bette S BLANCOl, Jorge C Pollard, John R |
| description | 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.
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.
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. |
| doi_str_mv | 10.21873/invivo.12221 |
| format | Article |
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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.
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.</description><identifier>ISSN: 0258-851X</identifier><identifier>EISSN: 1791-7549</identifier><identifier>DOI: 10.21873/invivo.12221</identifier><identifier>PMID: 33144490</identifier><language>eng</language><publisher>Greece: International Institute of Anticancer Research</publisher><subject>Animals ; Betacoronavirus - pathogenicity ; Coronavirus Infections - complications ; Coronavirus Infections - drug therapy ; Coronavirus Infections - pathology ; Coronavirus Infections - virology ; COVID-19 ; Cytokines - biosynthesis ; Cytokines - genetics ; Digitoxin - pharmacology ; Disease Models, Animal ; Humans ; Influenza, Human - drug therapy ; Influenza, Human - metabolism ; Influenza, Human - virology ; Lung - pathology ; Lung - virology ; Male ; NF-kappa B - genetics ; Pandemics ; Pneumonia, Viral - complications ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - pathology ; Pneumonia, Viral - virology ; Prostatic Neoplasms - complications ; Prostatic Neoplasms - drug therapy ; Prostatic Neoplasms - pathology ; Prostatic Neoplasms - virology ; Rats ; SARS-CoV-2 ; Tumor Necrosis Factor-alpha - genetics</subject><ispartof>In vivo (Athens), 2020-11, Vol.34 (6), p.3723-3730</ispartof><rights>Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.</rights><rights>Copyright 2020, International Institute of Anticancer Research 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c387t-490af204e5ed029d28c5c08c75c04527dd70e31abf86f73987114253ef1f7fd3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811644/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7811644/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,727,780,784,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33144490$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pollard, Bette S</creatorcontrib><creatorcontrib>BLANCOl, Jorge C</creatorcontrib><creatorcontrib>Pollard, John R</creatorcontrib><title>Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy</title><title>In vivo (Athens)</title><addtitle>In Vivo</addtitle><description>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.
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.
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.</description><subject>Animals</subject><subject>Betacoronavirus - pathogenicity</subject><subject>Coronavirus Infections - complications</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - pathology</subject><subject>Coronavirus Infections - virology</subject><subject>COVID-19</subject><subject>Cytokines - biosynthesis</subject><subject>Cytokines - genetics</subject><subject>Digitoxin - pharmacology</subject><subject>Disease Models, Animal</subject><subject>Humans</subject><subject>Influenza, Human - drug therapy</subject><subject>Influenza, Human - metabolism</subject><subject>Influenza, Human - virology</subject><subject>Lung - pathology</subject><subject>Lung - virology</subject><subject>Male</subject><subject>NF-kappa B - genetics</subject><subject>Pandemics</subject><subject>Pneumonia, Viral - complications</subject><subject>Pneumonia, Viral - drug therapy</subject><subject>Pneumonia, Viral - pathology</subject><subject>Pneumonia, Viral - virology</subject><subject>Prostatic Neoplasms - complications</subject><subject>Prostatic Neoplasms - drug therapy</subject><subject>Prostatic Neoplasms - pathology</subject><subject>Prostatic Neoplasms - virology</subject><subject>Rats</subject><subject>SARS-CoV-2</subject><subject>Tumor Necrosis Factor-alpha - genetics</subject><issn>0258-851X</issn><issn>1791-7549</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkUFrGzEQhUVJqZ20x16DjjlkU42ktbSXQlg3rSHQQwzpTci7kq10V3IkrYn767vETkguMwPzzZthHkJfgVxRkIJ9c37nduEKKKXwAU1BVFCIklcnaEpoKQtZwp8JOk3pgZCZIIR-QhPGgHNekSla1Z1OyTW6w_M4rPHcrV0OT87jhd-4lctpLGw3GP9P43qfw1_nDb7LIfaX-N7lDV70226czy74hG2IuA471xZQ4eXGRL3df0Yfre6S-XLMZ2h582NZ_ypuf_9c1Ne3RcOkyMV4jraUcFOaltCqpbIpGyIbMUZeUtG2ghgGemXlzApWSQHAacmMBStsy87Q94Psdlj1pm2Mz1F3ahtdr-NeBe3U-453G7UOOyUkwIzzUeDiKBDD42BSVr1Ljek67U0YkqK8FLMKxq-PaHFAmxhSisa-rgGinm1RB1vUsy0jf_72tlf6xQf2H0X_i20</recordid><startdate>20201101</startdate><enddate>20201101</enddate><creator>Pollard, Bette S</creator><creator>BLANCOl, Jorge C</creator><creator>Pollard, John R</creator><general>International Institute of Anticancer Research</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20201101</creationdate><title>Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy</title><author>Pollard, Bette S ; BLANCOl, Jorge C ; Pollard, John R</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c387t-490af204e5ed029d28c5c08c75c04527dd70e31abf86f73987114253ef1f7fd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Betacoronavirus - pathogenicity</topic><topic>Coronavirus Infections - complications</topic><topic>Coronavirus Infections - drug therapy</topic><topic>Coronavirus Infections - pathology</topic><topic>Coronavirus Infections - virology</topic><topic>COVID-19</topic><topic>Cytokines - biosynthesis</topic><topic>Cytokines - genetics</topic><topic>Digitoxin - pharmacology</topic><topic>Disease Models, Animal</topic><topic>Humans</topic><topic>Influenza, Human - drug therapy</topic><topic>Influenza, Human - metabolism</topic><topic>Influenza, Human - virology</topic><topic>Lung - pathology</topic><topic>Lung - virology</topic><topic>Male</topic><topic>NF-kappa B - genetics</topic><topic>Pandemics</topic><topic>Pneumonia, Viral - complications</topic><topic>Pneumonia, Viral - drug therapy</topic><topic>Pneumonia, Viral - pathology</topic><topic>Pneumonia, Viral - virology</topic><topic>Prostatic Neoplasms - complications</topic><topic>Prostatic Neoplasms - drug therapy</topic><topic>Prostatic Neoplasms - pathology</topic><topic>Prostatic Neoplasms - virology</topic><topic>Rats</topic><topic>SARS-CoV-2</topic><topic>Tumor Necrosis Factor-alpha - genetics</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Pollard, Bette S</creatorcontrib><creatorcontrib>BLANCOl, Jorge C</creatorcontrib><creatorcontrib>Pollard, John R</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>In vivo (Athens)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pollard, Bette S</au><au>BLANCOl, Jorge C</au><au>Pollard, John R</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy</atitle><jtitle>In vivo (Athens)</jtitle><addtitle>In Vivo</addtitle><date>2020-11-01</date><risdate>2020</risdate><volume>34</volume><issue>6</issue><spage>3723</spage><epage>3730</epage><pages>3723-3730</pages><issn>0258-851X</issn><eissn>1791-7549</eissn><abstract>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.
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.
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.</abstract><cop>Greece</cop><pub>International Institute of Anticancer Research</pub><pmid>33144490</pmid><doi>10.21873/invivo.12221</doi><tpages>8</tpages><oa>free_for_read</oa></addata></record> |
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| source | MEDLINE; Elektronische Zeitschriftenbibliothek - Frei zugängliche E-Journals; PubMed Central |
| subjects | Animals Betacoronavirus - pathogenicity Coronavirus Infections - complications Coronavirus Infections - drug therapy Coronavirus Infections - pathology Coronavirus Infections - virology COVID-19 Cytokines - biosynthesis Cytokines - genetics Digitoxin - pharmacology Disease Models, Animal Humans Influenza, Human - drug therapy Influenza, Human - metabolism Influenza, Human - virology Lung - pathology Lung - virology Male NF-kappa B - genetics Pandemics Pneumonia, Viral - complications Pneumonia, Viral - drug therapy Pneumonia, Viral - pathology Pneumonia, Viral - virology Prostatic Neoplasms - complications Prostatic Neoplasms - drug therapy Prostatic Neoplasms - pathology Prostatic Neoplasms - virology Rats SARS-CoV-2 Tumor Necrosis Factor-alpha - genetics |
| title | Classical Drug Digitoxin Inhibits Influenza Cytokine Storm, With Implications for Covid-19 Therapy |
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