title: Analysis of bronchoalveolar lavage fluid in a mouse model of bronchial asthma and H1N1 2009 infection.
abstract: BACKGROUND
  Bronchial asthma is known as a risk factor of admission to the intensive care unit. However, the mechanism by which pandemic 2009 H1N1 (A(H1N1)pdm09) infection increases the severity of symptoms in patients with bronchial asthma is unknown; therefore, we aimed at determining this mechanism.
  
  
  METHODS
  Inflammatory cell levels in the bronchoalveolar lavage (BAL) fluid from the non-asthma/mock, non-asthma/A(H1N1)pdm09, asthma/mock, and asthma/A(H1N1)pdm09 groups were determined using BALB/c mice. Cell infiltration levels, cytokine levels, and viral titers were compared among the groups.
  
  
  RESULTS
  Neutrophil, monocyte, interleukin (IL)-5, IL-6, IL-10, IL-13, and tumor necrosis factor (TNF)-α levels were significantly higher in the BAL fluid from the non-asthma/A(H1N1)pdm09 and asthma/A(H1N1)pdm09 groups than in the mock groups (p<0.05 for neutrophils and monocytes; p<0.01 for the rest). The number of eosinophils and CD8(+) lymphocytes and the level of transforming growth factor beta 1 (TGF-β1) in BAL fluid in the asthma/A(H1N1)pdm09 group were significantly higher among all groups (p<0.05 for eosinophils and CD8(+) lymphocytes; p<0.01 for TGF-β1). The levels of IL-6, IL-10, IL-13, and TNF-α were significantly higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05 for IL-6 and IL-10; p<0.01 for IL-13 and TNF-α). The level of IFN-γ in the asthma/A(H1N1)pdm09 group was significantly lower than that in the non-asthma/A(H1N1)pdm09 group (p<0.05). The viral titers in the BAL fluids were higher in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group (p<0.05). Histopathological examination showed more severe infiltration of inflammatory cells and destruction of lung tissue in the asthma/A(H1N1)pdm09 group than in the non-asthma/A(H1N1)pdm09 group.
  
  
  CONCLUSIONS
  Severe pulmonary inflammation induced by elevated levels of cytokines, combined with increased viral replication due to decreased IFN-γ levels, may contribute to worsening respiratory symptoms in patients with bronchial asthma and A(H1N1)pdm09 infection.
authors.affiliation: Department of Pediatrics, Yamaguchi University Graduate School of Medicine, 1-1-1 Minamikogushi, Ube, Yamaguchi 755-8505, Japan. p002um@yamaguchi-u.ac.jp
authors.forename: Seigo
authors.initials: S
authors.lastname: Okada
authors.forename: Shunji
authors.initials: S
authors.lastname: Hasegawa
authors.forename: Hideki
authors.initials: H
authors.lastname: Hasegawa
authors.forename: Akira
authors.initials: A
authors.lastname: Ainai
authors.forename: Ryo
authors.initials: R
authors.lastname: Atsuta
authors.forename: Kenzo
authors.initials: K
authors.lastname: Ikemoto
authors.forename: Kohsuke
authors.initials: K
authors.lastname: Sasaki
authors.forename: Shoichi
authors.initials: S
authors.lastname: Toda
authors.forename: Komei
authors.initials: K
authors.lastname: Shirabe
authors.forename: Midori
authors.initials: M
authors.lastname: Takahara
authors.forename: Sawako
authors.initials: S
authors.lastname: Harada
authors.forename: Tsuneo
authors.initials: T
authors.lastname: Morishima
authors.forename: Takashi
authors.initials: T
authors.lastname: Ichiyama
mesh_terms: D000818:Animals; D001249:Asthma / Q000378:metabolism*; D001992:Bronchoalveolar Lavage Fluid / Q000166:cytology / Q000276:immunology*; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D053118:Influenza A Virus, H1N1 Subtype; D016753:Interleukin-10 / Q000378:metabolism; D018793:Interleukin-13 / Q000378:metabolism; D015848:Interleukin-5 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D008168:Lung / Q000378:metabolism; D018655:Lymphocyte Count; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000276:immunology; D009504:Neutrophils / Q000276:immunology; D009976:Orthomyxoviridae Infections / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D018793:Interleukin-13; D015848:Interleukin-5; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10