title: The effect of rosuvastatin in a murine model of influenza A infection.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Northwestern University Feinberg School of Medicine, Chicago, Illinois, United States of America. k-radigan@northwestern.edu
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: Radigan
authors.forename: Daniela
authors.initials: D
authors.lastname: Urich
authors.forename: Alexander V
authors.initials: AV
authors.lastname: Misharin
authors.forename: Sergio E
authors.initials: SE
authors.lastname: Chiarella
authors.forename: Saul
authors.initials: S
authors.lastname: Soberanes
authors.forename: Angel
authors.initials: A
authors.lastname: Gonzalez
authors.forename: Harris
authors.initials: H
authors.lastname: Perlman
authors.forename: Richard G
authors.initials: RG
authors.lastname: Wunderink
authors.forename: G R Scott
authors.initials: GR
authors.lastname: Budinger
authors.forename: Gökhan M
authors.initials: GM
authors.lastname: Mutlu
mesh_terms: D000818:Animals; D000998:Antiviral Agents / Q000494:pharmacology*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002460:Cell Line; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D005464:Fluorobenzenes / Q000494:pharmacology*; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D053118:Influenza A Virus, H1N1 Subtype / Q000187:drug effects* / Q000502:physiology; D053122:Influenza A Virus, H3N2 Subtype / Q000187:drug effects* / Q000502:physiology; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology / Q000821:virology; D008264:Macrophages / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D011014:Pneumonia / Q000188:drug therapy / Q000378:metabolism / Q000821:virology; D011743:Pyrimidines / Q000494:pharmacology*; D000068718:Rosuvastatin Calcium; D013449:Sulfonamides / Q000494:pharmacology*; D014779:Virus Replication / Q000187:drug effects
chemical_list: D000998:Antiviral Agents; D016207:Cytokines; D005464:Fluorobenzenes; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D011743:Pyrimidines; D013449:Sulfonamides; D000068718:Rosuvastatin Calcium