Acute respiratory distress syndrome induced by avian influenza A (H5N1) virus in mice

Rationale and Objective: The acute respiratory distress syndrome (ARDS) caused by avian influenza H5N1 viral infection has been reported in many humans since this virus was found to infect humans in Hong Kong in 1997, but no studies regarding an animal model of ARDS with H5N1 viral infection have been found in the literature. Here we present a mouse model of ARDS induced by H5N1 virus. Methods: Six- to 8-wk-old BALB/c mice were inoculated intranasally (50 mu l) with 1 X 10(2) 50% mouse infectious doses of A/Chicken/ Hebei/108/2002 (H5N1) virus. Lung injury was assessed by observation of lung water content and histopathology. Arterial blood gas, white blood cell count in bronchial alveolar lavage fluid, and tumor necrosis factor-alpha and interleukin-6 in bronchoalveolar lavage fluid and serum were measured at the indicated time points. Results: Our data showed that H5N1 viral infection in mice resulted in typical ARDS, which was characterized by the following features: (1) about 80% of mice (13 of 16) dead on Days 6 to 8 postinoculation; (2) highly edematous lungs and dramatically increased lung wet:dry weight ratios and lung wet weight:body weight ratios; (3) inflammatory cellular infiltration, alveolar and interstitial edema, and hemorrhage in lungs; (4) progressive and severe hypoxemia; and (5) significant increase in neutrophils, tumor necrosis factor-alpha, and interleukin-6 in BALF. Conclusion: These results suggested that we successfully established a mouse model of ARDS with H5N1 viral infection, which may benefit further investigation into the pathogenesis of human ARDS induced by H5N1 virus.