Corticosteroid Treatment Ameliorates Acute Lung Injury Induced by 2009 Swine Origin Influenza A (H1N1) Virus in Mice

Abstract

BackgroundThe 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 FindingsWe 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/SignificanceUsing 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.

Effect of low‐to‐moderate‐dose corticosteroids on mortality of hospitalized adolescents and adults with influenza A(H1N1)pdm09 viral pneumonia

“…The use of corticosteroids is based on the underlying pathogenesis of severe influenza infection, which is characterized by overproduction of proinflammatory cytokines/chemokines and an excess of activated lymphocytes, which may result in severe lung damage and delayed recovery . Moreover, animal model studies also found that corticosteroid treatment decreased mortality and ameliorated the acute lung injury induced by influenza A(H1N1)pdm09 virus . Although corticosteroids are posited to be beneficial in the treatment of severe influenza patients, clinical results remain contradictory and opposition overwhelms support in studies published so far .…”

Monoclonal antibody against CXCL-10/IP-10 ameliorates influenza A (H1N1) virus induced acute lung injury

“…Although corticosteroid was shown effective in treating mouse ALI induced by 2009 S-OIV H1N1 infection [12], modulation of the host immune response with less selective pressure on viral populations is enticing. MDX-1100, a fully human anti-IP-10 monoclonal antibody, is well tolerated and demonstrated clinical efficacy in patients with rheumatoid arthritis who responded inadequately to Methotrexate in a phase II, randomized, double-blind, placebo-controlled study [13].…”

Re-understanding anti-influenza strategy: attach equal importance to antiviral and anti-inflammatory therapies

“…The use of glucocorticoids in the treatment of severe viral pneumonia has come from the experience of SARS treatment in Guangzhou, China. SARS coronavirus induces a IFN-γ-related cytokine storm in patients, which might be involved in the immunopathological damage observed in patients with SARS (81). A retrospective study of Guangzhou SARS cases showed that corticosteroid use reduced mortality and shortened hospitalization (82).…”