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Published ahead of print on August 17, 2006, doi:10.1164/rccm.200511-1751OC

Am. J. Respir. Crit. Care Med., Volume 174, Number 9, November 2006, 1011-1017

A more recent version of this article appeared on November 1, 2006
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Submitted on November 15, 2005
Accepted on August 16, 2006

Acute Respiratory Distress Syndrome Induced by Avian Influenza A (H5N1) Virus in Mice

Tong Xu1, Jian Qiao1*, Lihong Zhao1, Guirong Wang1, Guimei He1, Kai Li1, Yong Tian1, Mingyu Gao1, Jianlin Wang1, Huiyu Wang1, and Changgui Dong1

1 Department of Pathophysiology, College of Veterinary Medicine, China Agricultural University, Beijing, China

* To whom correspondence should be addressed. E-mail: qiaojian{at}cau.edu.cn.

Rationale and Objective: The acute respiratory distress syndrome (ARDS) caused by avian influenza H5N1 virus infection has been reported in many human cases since this virus was found to infect to human in Hong Kong in 1997, but no studies regarding the animal model of ARDS with H5N1 virus infection can be found in literature. Here we present a mouse model of ARDS induced by H5N1 virus. Methods: Six to eight weeks old Balb/c mice were inoculated intranasally (50µl) with 1x102 fifty percent mouse infectious doses of A/Chicken/ Hebei/108/2002(H5N1) virus. Lung injury was assessed by observation of lung water content and histopathology. The content of arterial blood gas, the white blood cell counts in bronchial alveolar lavage fluid (BALF) and the TNF-{alpha} and IL-6 in BALF and serum were measured at indicated time points. Results: Our data showed that H5N1 virus infection in mice resulted in the typical ARDS, which was characterized by the following features: (i) about eighty percent of mice (13/16) dead on days 6 to 8 postinoculation; (ii) highly edematous lungs and dramatically increased lung wet-to-dry weight ratios and lung wet weight/body weight ratios; (iii) inflammatory cellular infiltration, alveolar and interstitial edema and hemorrhage in lungs; (iv) the progressive and severe hypoxemia; (v) the significant increase of neutrophils, TNF-{alpha} and IL-6 in BALF. Conclusion: These results suggested that we successfully established a mouse model of ARDS with H5N1 virus infection, which may benefit further investigation into the pathogenesis of human ARDS induced by H5N1 virus.
Key words: Acute Respiratory Distress Syndrome, Avian Influenza A H5N1 Virus, Cytokine




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