5 Models of ARDS ARDS is characterized by a localized hyperinflammatory response to an infectious agent in the lung, resulting in damage to the alveolus–capillary interface (Hammerbeck et al., 2007). H5N1 virus-infected humans initially present with clinical signs of influenza-like illness, then develop progressive pneumonia and may eventually die of ARDS (Grose and Chokephaibulkit, 2004). Thus, some research has been done to develop a model of ARDS in H5N1 virus-infected mice. In one ARDS model using six to eight-week-old BALB/c mice inoculated intranasally with influenza virus A H5N1 (A/Chicken/Hebei/108/2002), the animals developed typical ARDS, with highly edematous lungs, dramatic increases in lung weights, progressively more hypoxemia and 80% mortality by day 8 (Xu et al., 2006). Histological examination revealed inflammatory cell infiltrates in the alveoli with a significant increase in neutrophils, interstitial edema and hemorrhage. Levels of TNF-α and L-6 in bronchiolar lavage fluids were significantly increased. The model thus displayed some of the more significant signs and symptoms associated with ARDS in humans. A summary of current animal models available for studying ARDS in H5N1 influenza is shown in Table 6 . Table 6 Summary of current animal models available for studying acute respiratory distress syndrome (ARDS) developing in the setting of H5N1 avian influenza. Virus Animal Model References Influenza A H5N1 Mouse (BALB/c) Xu et al. (2006) A/Chicken/Hebei/108/2002 Influenza A H5N1 Cynomolgus macaques Kuiken et al. (2003) A/HongKong/156/97 Rimmelzwaan et al. (2003)