Abstract
BackgroundThe avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Avian influenza is characterized by pronounced activation of the proinflammatory cytokine cascade, which perpetuates the inflammatory response, leading to persistent systemic inflammatory response syndrome and pulmonary infection in animals and humans. There are currently no specific treatment strategies for avian influenza.MethodsWe hypothesized that mesenchymal stromal cells (MSCs) would have beneficial effects in the treatment of H9N2 AIV-induced acute lung injury in mice. Six- to 8-week-old C57BL/6 mice were infected intranasally with 1 × 104 MID50 of A/HONG KONG/2108/2003 [H9N2 (HK)] H9N2 virus to induce acute lung injury. After 30 min, syngeneic MSCs were delivered through the caudal vein. Three days after infection, we measured the survival rate, lung weight, arterial blood gas, and cytokines in both bronchoalveolar lavage fluid (BALF) and serum, and assessed pathological changes to the lungs.ResultsMSC administration significantly palliated H9N2 AIV-induced pulmonary inflammation by reducing chemokines and proinflammatory cytokines levels, as well as reducing inflammatory cell recruit into the lungs. Thus, H9N2 AIV-induced lung injury was markedly alleviated in mice treated with MSCs. Lung histopathology and arterial blood gas analysis were improved in mice with H9N2 AIV-induced lung injury following MSC treatment.ConclusionsMSC treatment significantly reduces H9N2 AIV-induced acute lung injury in mice and is associated with reduced pulmonary inflammation. These results indicate a potential role for MSC therapy in the treatment of clinical avian influenza.
Highlights
The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans
Virus titration in the lungs of mice H9N2 viral infection resulted in high viral titers in the lungs; the viral titers of the H9N2 infected mice + physiological saline group, H9N2 infected mice + McCoy group, and H9N2 infected mice + Mesenchymal stromal cell (MSC) group exceeded 6.0 log10 EID50/ml (Fig. 3) on day 3 post-infection
Compared with the H9N2 infected mice + physiological saline and H9N2 infected mice + McCoy groups, mice in the H9N2 infected + MSCs group had significantly higher PaO2, significantly lower PaCO2, and slightly higher SaO2 and pH values. These results indicate that most of the H9N2 AIV infected mice developed severe hypoxemia, and that MSCs effectively protected against functional pulmonary injury
Summary
The avian influenza virus (AIV) can cross species barriers and expand its host range from birds to mammals, even humans. Infections with avian influenza virus (AIV) strains have become highly prevalent in poultry worldwide [1,2,3,4]. The H9N2 strain has been isolated from pigs and humans with influenza-like illnesses in Hong Kong and mainland China since 1998 [9, 10]. These findings indicate that the AIV can cross species barriers and expand its host range from birds to mammals, highlighting the pandemic potential of the H9N2 virus
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