Corticosteroid treatment ameliorates acute lung injury induced by 2009 swine origin influenza A (H1N1) virus in mice

PLoS One. 2012;7(8):e44110. doi: 10.1371/journal.pone.0044110. Epub 2012 Aug 29.

Abstract

Background: The 2009 influenza pandemic affected people in almost all countries in the world, especially in younger age groups. During this time, the debate over whether to use corticosteroid treatment in severe influenza H1N1 infections patients resurfaced and was disputed by clinicians. There is an urgent need for a susceptible animal model of 2009 H1N1 infection that can be used to evaluate the pathogenesis and the therapeutic effect of corticosteroid treatment during infection.

Methodology/principal findings: We intranasally inoculated two groups of C57BL/6 and BALB/c mice (using 4- or 6-to 8-week-old mice) to compare the pathogenesis of several different H1N1 strains in mice of different ages. Based on the results, a very susceptible 4-week-old C57BL/6 mouse model of Beijing 501 strain of 2009 H1N1 virus infection was established, showing significantly elevated lung edema and cytokine levels compared to controls. Using our established animal model, the cytokine production profile and lung histology were assessed at different times post-infection, revealing increased lung lesions in a time-dependent manner. In additional,the mice were also treated with dexamethasone, which significantly improved survival rate and lung lesions in infected mice compared to those in control mice. Our data showed that corticosteroid treatment ameliorated acute lung injury induced by the 2009 A/H1N1 virus in mice and suggested that corticosteroids are valid drugs for treating 2009 A/H1N1 infection.

Conclusions/significance: Using the established, very susceptible 2009 Pandemic Influenza A (H1N1) mouse model, our studies indicate that corticosteroids are a potential therapeutic remedy that may address the increasing concerns over future 2009 A/H1N1 pandemics.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acute Lung Injury / drug therapy*
  • Acute Lung Injury / immunology
  • Acute Lung Injury / pathology
  • Acute Lung Injury / virology*
  • Adrenal Cortex Hormones / administration & dosage
  • Adrenal Cortex Hormones / pharmacology
  • Adrenal Cortex Hormones / therapeutic use*
  • Animals
  • Cytokines / metabolism
  • Dexamethasone / administration & dosage
  • Dexamethasone / pharmacology
  • Dexamethasone / therapeutic use
  • Disease Models, Animal
  • Inflammation / complications
  • Inflammation / pathology
  • Inflammation / virology
  • Influenza A Virus, H1N1 Subtype / drug effects
  • Influenza A Virus, H1N1 Subtype / physiology*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Inbred C57BL
  • Orthomyxoviridae Infections / drug therapy*
  • Orthomyxoviridae Infections / immunology
  • Orthomyxoviridae Infections / pathology
  • Orthomyxoviridae Infections / virology*
  • Sus scrofa / virology*
  • Weaning

Substances

  • Adrenal Cortex Hormones
  • Cytokines
  • Dexamethasone

Grant support

Funding provided by National Natural Scientific Foundation (30800977 and 30972614) (http://www.nsfc.gov.cn/Portal0/default106.htm), Beijing Natural Science Foundation (7112105) (http://www.bjnsf.org/) and Ministry of Science and Technology of China (2009CB522102 and 2009CB522105) (http://www.973.gov.cn/Default_3.aspx) 111project (B08007) (http://www.safea.gov.cn/english/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.