title: Preventive effect of G-CSF on acute lung injury via alveolar macrophage regulation.
abstract: BACKGROUND
  Acute lung injury and acute respiratory distress syndrome (ALI/ARDS) are devastating clinical syndromes associated with a high mortality rate. We examined the preventive effect of recombinant human granulocyte colony-stimulating factor (rhG-CSF) in a mouse ALI/ARDS model induced by lipopolysaccharide (LPS).
  
  
  METHODS
  Mice were injected with LPS (10-20 mg/kg) with or without rhG-CSF pretreatment (250 mg/kg/d). Survival rate, cytokine mRNA expression, and pathologic findings were examined.
  
  
  RESULTS
  The 96-h survival rate of the control group was 20%. Survival was significantly increased to 80% in rhG-CSF-treated animals. LPS-induced destruction of the alveolar structure was not observed in the rhG-CSF group. Pretreatment with rhG-CSF led to significantly lower mRNA expression of TNF-α and IL-1β in the lung 24 h after LPS administration and significantly higher IL-10 expression 96 h after LPS administration. Immunohistochemical analysis revealed that treatment with rhG-CSF also prevented the up-regulation of TNF-α and IL-1β protein expression in alveolar macrophages.
  
  
  CONCLUSIONS
  Treatment with rhG-CSF prevents the development of ALI/ARDS induced by LPS by affecting the production of pro- and anti-inflammatory cytokines and may be promising in clinical applications.
authors.affiliation: Department of Surgery, Division of Frontier Medical Science, Programs for Biomedical Research, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Yamaguchi
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyata
authors.forename: Keisuke
authors.initials: K
authors.lastname: Hayamizu
authors.forename: Jun
authors.initials: J
authors.lastname: Hashizume
authors.forename: Tomio
authors.initials: T
authors.lastname: Matsumoto
authors.forename: Hirotaka
authors.initials: H
authors.lastname: Tashiro
authors.forename: Hideki
authors.initials: H
authors.lastname: Ohdan
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000276:immunology* / Q000401:mortality / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology*; D006801:Humans; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000276:immunology* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011650:Pulmonary Alveoli / Q000187:drug effects / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D012128:Respiratory Distress Syndrome / Q000188:drug therapy / Q000276:immunology / Q000401:mortality / Q000517:prevention & control; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D016179:Granulocyte Colony-Stimulating Factor