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


CONCLUSIONS
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.
Xu
Tong
T
Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing, PR China.
Qiao
Jian
J
Zhao
Lihong
L
Wang
Guirong
G
He
Guimei
G
Li
Kai
K
Tian
Yong
Y
Gao
Mingyu
M
Wang
Jianlin
J
Wang
Huiyu
H
Dong
Changgui
C
D000818:Animals; D001772:Blood Cell Count; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology; D004195:Disease Models, Animal; D005260:Female; D053124:Influenza A Virus, H5N1 Subtype; D015850:Interleukin-6 / Q000032:analysis; D051379:Mice; D008807:Mice, Inbred BALB C; D009976:Orthomyxoviridae Infections / Q000097:blood / Q000150:complications* / Q000473:pathology; D012128:Respiratory Distress Syndrome / Q000097:blood / Q000473:pathology / Q000821:virology*; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha