Anti-IFN-γ therapy alleviates acute lung injury induced by severe influenza A (H1N1) pdm09 infection in mice.

Abstract

Severe infection with influenza A (H1N1)pdm09 virus is characterized by acute lung injury. The limited efficacy of anti-viral drugs indicates an urgent need for additional therapies. We have previously reported that neutralization of gamma interferon (IFN-γ) could significantly rescue the thymic atrophy induced by severe influenza A (H1N1)pdm09 infection in BALB/c mice. A deeper investigation was conducted into the influence of neutralizing IFN-γ to the BALB/c mice weight, survival rate, and lung injury. The BALB/c mice was infected with severe influenza A (H1N1)pdm09. Monoclonal antibodies against IFN-γ were injected into the abdominal cavities of the mice. After neutralization of IFN-γ occurred in mice infected by severe ∖ influenza A (H1N1)pdm09, observing the influence of neutralizing IFN-γ to the BALB/c mice weight, survival rate, lung injury. Our results here showed that anti-IFN-γ therapy alleviated the acute lung injury in this mouse model. Neutralization of IFN-γ led to a significant reduction in the lung microvascular leak and the cellular infiltrate in the lung tissue, and also improved the outcome in mice mortality. Several pro-inflammatory cytokines, including interleukin (IL)-1α, tumor necrosis factor (TNF)-α and granulocyte-colony stimulating factor (G-CSF) in the bronchoalveolar lavage fluid (BALF), and the chemokines including G-CSF, monocyte chemoattractant protein-1 (MCP-1) in serum samples were found to be significantly reduced after anti-IFN-γ treatment. These results suggested that IFN-γ plays an important role in acute lung injury induced by severe influenza A (H1N1)pdm09 infection, and monoclonal antibodies against IFN-γ could be useful as a potential therapeutic remedy for future influenza pandemics.