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

Abstract

RATIONALE:

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: 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
• Journal: PloS one (PLoS One) Vol. 7 Issue 4 Pg. e35788 ( 2012) ISSN: 1932-6203 [Electronic] United States
• PMID: 22536437 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)

Chemical References

• Antiviral Agents
• Cytokines
• Fluorobenzenes
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• Pyrimidines
• Sulfonamides
• Rosuvastatin Calcium

Topics

• Animals
• Antiviral Agents (pharmacology)
• Bronchoalveolar Lavage Fluid (chemistry)
• Cell Line
• Cytokines (metabolism)
• Disease Models, Animal
• Fluorobenzenes (pharmacology)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Influenza A Virus, H1N1 Subtype (drug effects, physiology)
• Influenza A Virus, H3N2 Subtype (drug effects, physiology)
• Lung (drug effects, metabolism, pathology, virology)
• Macrophages (metabolism, pathology)
• Male
• Mice
• Mice, Inbred C57BL
• Orthomyxoviridae Infections (drug therapy, pathology, virology)
• Pneumonia (drug therapy, metabolism, virology)
• Pyrimidines (pharmacology)
• Rosuvastatin Calcium
• Sulfonamides (pharmacology)
• Virus Replication (drug effects)