The effect of rosuvastatin in a murine model of influenza A infection.

<h4>Rationale</h4>HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortal...

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Autores principales: Kathryn A Radigan, Daniela Urich, Alexander V Misharin, Sergio E Chiarella, Saul Soberanes, Angel Gonzalez, Harris Perlman, Richard G Wunderink, G R Scott Budinger, Gökhan M Mutlu
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spelling oai:doaj.org-article:e1610579da42473e908243a65e720c162021-11-18T07:21:22ZThe effect of rosuvastatin in a murine model of influenza A infection.1932-620310.1371/journal.pone.0035788https://doaj.org/article/e1610579da42473e908243a65e720c162012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22536437/?tool=EBIhttps://doaj.org/toc/1932-6203<h4>Rationale</h4>HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza A infection in mice.<h4>Methods</h4>C57Bl/6 mice were treated daily with rosuvastatin (10 mg/kg/day) supplemented in chow (or control chow) beginning three days prior to infection with either A//Udorn/72 [H3N2] or A/WSN/33 [H1N1] influenza A virus (1×10(5) pfu/mouse). Plaque assays were used to examine the effect of rosuvastatin on viral replication in vitro and in the lungs of infected mice. We measured cell count with differential, protein and cytokines in the bronchoalveolar lavage (BAL) fluid, histologic evidence of lung injury, and wet-to-dry ratio on Day 1, 2, 4, and 6. We also recorded daily weights and mortality.<h4>Results</h4>The administration of rosuvastatin had no effect on viral clearance of influenza A after infection. Weight loss, lung inflammation and lung injury severity were similar in the rosuvastatin and control treated mice. In the mice infected with influenza A (A/WSN/33), mortality was unaffected by treatment with rosuvastatin.<h4>Conclusions</h4>Statins did not alter the replication of influenza A in vitro or enhance its clearance from the lung in vivo. Statins neither attenuated the severity of influenza A-induced lung injury nor had an effect on influenza A-related mortality. Our data suggest that the association between HMG CoA reductase inhibitors and improved outcomes in patients with sepsis and pneumonia are not attributable to their effects on influenza A infection.Kathryn A RadiganDaniela UrichAlexander V MisharinSergio E ChiarellaSaul SoberanesAngel GonzalezHarris PerlmanRichard G WunderinkG R Scott BudingerGökhan M MutluPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35788 (2012)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Kathryn A Radigan
Daniela Urich
Alexander V Misharin
Sergio E Chiarella
Saul Soberanes
Angel Gonzalez
Harris Perlman
Richard G Wunderink
G R Scott Budinger
Gökhan M Mutlu
The effect of rosuvastatin in a murine model of influenza A infection.
description <h4>Rationale</h4>HMG-CoA reductase inhibitors such as rosuvastatin may have immunomodulatory and anti-inflammatory effects that may reduce the severity of influenza A infection. We hypothesized that rosuvastatin would decrease viral replication, attenuate lung injury, and improve mortality following influenza A infection in mice.<h4>Methods</h4>C57Bl/6 mice were treated daily with rosuvastatin (10 mg/kg/day) supplemented in chow (or control chow) beginning three days prior to infection with either A//Udorn/72 [H3N2] or A/WSN/33 [H1N1] influenza A virus (1×10(5) pfu/mouse). Plaque assays were used to examine the effect of rosuvastatin on viral replication in vitro and in the lungs of infected mice. We measured cell count with differential, protein and cytokines in the bronchoalveolar lavage (BAL) fluid, histologic evidence of lung injury, and wet-to-dry ratio on Day 1, 2, 4, and 6. We also recorded daily weights and mortality.<h4>Results</h4>The administration of rosuvastatin had no effect on viral clearance of influenza A after infection. Weight loss, lung inflammation and lung injury severity were similar in the rosuvastatin and control treated mice. In the mice infected with influenza A (A/WSN/33), mortality was unaffected by treatment with rosuvastatin.<h4>Conclusions</h4>Statins did not alter the replication of influenza A in vitro or enhance its clearance from the lung in vivo. Statins neither attenuated the severity of influenza A-induced lung injury nor had an effect on influenza A-related mortality. Our data suggest that the association between HMG CoA reductase inhibitors and improved outcomes in patients with sepsis and pneumonia are not attributable to their effects on influenza A infection.
format article
author Kathryn A Radigan
Daniela Urich
Alexander V Misharin
Sergio E Chiarella
Saul Soberanes
Angel Gonzalez
Harris Perlman
Richard G Wunderink
G R Scott Budinger
Gökhan M Mutlu
author_facet Kathryn A Radigan
Daniela Urich
Alexander V Misharin
Sergio E Chiarella
Saul Soberanes
Angel Gonzalez
Harris Perlman
Richard G Wunderink
G R Scott Budinger
Gökhan M Mutlu
author_sort Kathryn A Radigan
title The effect of rosuvastatin in a murine model of influenza A infection.
title_short The effect of rosuvastatin in a murine model of influenza A infection.
title_full The effect of rosuvastatin in a murine model of influenza A infection.
title_fullStr The effect of rosuvastatin in a murine model of influenza A infection.
title_full_unstemmed The effect of rosuvastatin in a murine model of influenza A infection.
title_sort effect of rosuvastatin in a murine model of influenza a infection.
publisher Public Library of Science (PLoS)
publishDate 2012
url https://doaj.org/article/e1610579da42473e908243a65e720c16
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