Corticosteroid Treatment Ameliorates Acute Lung Injury Induced by 2009 Swine Origin Influenza A (H1N1) Virus in Mice
Chenggang Li<SUP>1</SUP><SUP>#</SUP>, Penghui Yang<SUP>2</SUP><SUP>#</SUP>, Yanli Zhang<SUP>1</SUP><SUP>#</SUP>, Yang Sun<SUP>1</SUP>, Wei Wang<SUP>1</SUP>, Zhen Zou<SUP>1</SUP>, Li Xing<SUP>2</SUP>, Zhongwei Chen<SUP>2</SUP>, Chong Tang<SUP>2</SUP>, Feng Guo<SUP>1</SUP>, Jiejie Deng<SUP>1</SUP>, Yan Zhao<SUP>1</SUP>, Yiwu Yan<SUP>1</SUP>, Jun Tang<SUP>1</SUP>, Xiliang Wang<SUP>2</SUP><SUP>*</SUP>, Chengyu Jiang<SUP>1</SUP><SUP>*</SUP>
<SUP></SUP>
1 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College; Tsinghua University, Beijing, China, 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
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/H1N1pandemics.
Citation: Li C, Yang P, Zhang Y, Sun Y, Wang W, et al. (2012) Corticosteroid Treatment Ameliorates Acute Lung Injury Induced by 2009 Swine Origin Influenza A (H1N1) Virus in Mice. PLoS ONE 7(8): e44110. doi:10.1371/journal.pone.0044110
Editor: Sylvie Alonso, National University of Singapore, Singapore
Received: March 7, 2012; Accepted: July 30, 2012; Published: August 29, 2012
Copyright: ? 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: 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.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: jiang@pumc.edu.cn (CJ); xiliangw@126.com (XW)
# These authors contributed equally to this work.
-Chenggang Li<SUP>1</SUP><SUP>#</SUP>, Penghui Yang<SUP>2</SUP><SUP>#</SUP>, Yanli Zhang<SUP>1</SUP><SUP>#</SUP>, Yang Sun<SUP>1</SUP>, Wei Wang<SUP>1</SUP>, Zhen Zou<SUP>1</SUP>, Li Xing<SUP>2</SUP>, Zhongwei Chen<SUP>2</SUP>, Chong Tang<SUP>2</SUP>, Feng Guo<SUP>1</SUP>, Jiejie Deng<SUP>1</SUP>, Yan Zhao<SUP>1</SUP>, Yiwu Yan<SUP>1</SUP>, Jun Tang<SUP>1</SUP>, Xiliang Wang<SUP>2</SUP><SUP>*</SUP>, Chengyu Jiang<SUP>1</SUP><SUP>*</SUP>
<SUP></SUP>
1 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Department of Biochemistry and Molecular Biology, Peking Union Medical College; Tsinghua University, Beijing, China, 2 State Key Laboratory of Pathogen and Biosecurity, Beijing Institute of Microbiology and Epidemiology, Beijing, China
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/H1N1pandemics.
Citation: Li C, Yang P, Zhang Y, Sun Y, Wang W, et al. (2012) Corticosteroid Treatment Ameliorates Acute Lung Injury Induced by 2009 Swine Origin Influenza A (H1N1) Virus in Mice. PLoS ONE 7(8): e44110. doi:10.1371/journal.pone.0044110
Editor: Sylvie Alonso, National University of Singapore, Singapore
Received: March 7, 2012; Accepted: July 30, 2012; Published: August 29, 2012
Copyright: ? 2012 Li et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Funding: 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.
Competing interests: The authors have declared that no competing interests exist.
* E-mail: jiang@pumc.edu.cn (CJ); xiliangw@126.com (XW)
# These authors contributed equally to this work.
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