Analysis of bronchoalveolar lavage fluid in a mouse model of bronchial asthma and H1N1 2009 infection
Introduction
The 2009 pandemic H1N1 (A(H1N1)pdm09) influenza virus originated in pigs and emerged among humans in Mexico during the spring of 2009 before spreading globally [1]. Most cases of A(H1N1)pdm09 infection involved mild symptoms, but some patients had severe respiratory problems such as severe pneumonia and acute respiratory distress syndrome (ARDS); these were particularly common in children and young adults [1], [2], [3], [4]. In children, bronchial asthma increases the risk of admission to the hospital and intensive care unit [4], [5], [6], [7]. A cytokine-mediated inflammatory response has been well documented in cases of pneumonia and ARDS [8], [9], [10], but to our knowledge, there are no published findings regarding the cytokine profile of bronchoalveolar lavage (BAL) fluid from patients who have bronchial asthma and are also infected by A(H1N1)pdm09. Thus, the mechanism by which A(H1N1)pdm09 infection increases the severity of symptoms in patients with bronchial asthma remains unclear.
In this study, we investigated the levels of cytokines and viral titers in BAL fluid in a mouse model of bronchial asthma with A(H1N1)pdm09 infection to determine the mechanism by which A(H1N1)pdm09 infection increases the severity of symptoms in mice with bronchial asthma.
Section snippets
Sensitization and allergen challenge of mice
BALB/c mice aged 6–8 weeks (Chiyoda Kaihatsu Co., Ltd., Tokyo, Japan) were sensitized and challenged with grade II ovalbumin (OVA; Sigma Chemical Co., St. Louis, MO, USA) or phosphate-buffered saline (PBS). For sensitization, mice were injected subcutaneously on days 0 and 14 with 50 μg OVA, which was dissolved in 300 μl PBS containing 2 mg aluminum hydroxide (alum; Wako Pure Chemical Industries, Ltd., Osaka, Japan). On days 22, 24, 26, and 28, the mice inhaled 1% (w/v) OVA in PBS for 30 min via a
Analysis of the cells in the BAL fluid
The number of inflammatory cells in the BAL fluid from the different groups is illustrated in Fig. 2. The number of neutrophils and monocytes in the non-asthma/A(H1N1)pdm09 and asthma/A(H1N1)pdm09 groups was significantly higher than that in the mock groups (all p < 0.05). The number of eosinophils in the asthma/mock group was significantly higher than that in the non-asthma/mock and non-asthma/A(H1N1)pdm09 groups (both p < 0.05), and the number of eosinophils in the asthma/A(H1N1)pdm09 groups was
Discussion
To our knowledge, this is the first report of BAL fluid analysis in A(H1N1)pdm09-infected mice with bronchial asthma. The results show that A(H1N1)pdm09 infection induces high levels of pro-inflammatory cytokines such as IL-6 and TNF-α in BAL fluid and that this increase is enhanced by the presence of bronchial asthma.
IL-6 and TNF-α are known as pro-inflammatory cytokines [11], [12], [13]. The levels of these cytokines are elevated in the sputum and BAL fluid of patients with asthma and are
Acknowledgements
This study was supported by Grants from the Ministry of Health, Labor and Welfare (H21-Shink-Ippan-010), Japan.
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