Involvement of oxidative stress in the pathogenesis of ARDS associated with viral pneumonia

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Nitric oxide(NO) and reactive oxygen species(ROS) have been suggested to be involved in the pathogenesis of ARDS. NO/ROS have also been reported to induce nitration of tyrosine and guanine leading to the formation of 3-nitrotyrosine(3-NT) and 8-nitro-cGMP, respectively. In this study, we found significant increase of 3-NT and 8-nitro-cGMP levels in the lungs of influenza virus(IFV)-infected mice. Strong induction of an antioxidant enzyme heme oxygenase-1 was also detected in the lung of infected mice. Upregulation of HO-1 in parallel with the formation of 8-nitro-cGMP suggested that formation of 8-nitro-cGMP or 3-NT may be involved in the oxidative stress responses in the IFV-infected mice. Therefore, we postulated that formation of 3-NT might also influence on the disease activity of ARDS in humans. We performed a case-control study for plasma 3-NT levels of ARDS patients with/without IFV infection and of control subjects. The ARDS patients with IFV infection had significantly higher 3-NT levels than the control subjects. Additionally, ARDS patients with high 3-NT levels had better survival rate compared to patients with low 3-NT levels. These data thus suggest that NO/ROS-mediated formation of 3-NT or 8-nitro-cGMP may be involved in a unique signal transduction contributing to the host defense or tissue repair against IFV-induced fulminant pneumonia/ARDS.