title: Pulmonary inflammation and emphysema: role of the cytokines IL-18 and IL-13.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is believed to be an inflammatory cytokine-driven disease, but a causal basis that can be associated with a specific cytokine has not been directly demonstrated. We have previously reported that proinflammatory cytokine IL-18 expression is important in the pathogenesis of pulmonary inflammation and lung injury in mice. Our results demonstrate that IL-18 overproduction in the lungs can induce lung diseases, such as pulmonary inflammation, lung fibrosis, and COPD.
  
  
  OBJECTIVE
  We analyzed the role of IL-18 in the pathogenesis of COPD.
  
  
  METHODS
  Using the human surfactant protein C promoter to drive expression of mature mouse IL-18 cDNA, we developed two different lines of transgenic (Tg) mice that overproduced mouse mature IL-18 in the lungs either constitutively or in response to doxycycline.
  
  
  RESULTS
  Constitutive overproduction of IL-18 in the lungs resulted in the increased production of IFN-gamma, IL-5, and IL-13, and chronic pulmonary lung inflammation with the appearance of CD8+ T cells, macrophages, neutrophils, and eosinophils. Increased lung volume, severe emphysematous change, dilatation of the right ventricle, and mild pulmonary hypertension were observed in (more than 15-wk-old) Tg mice. Interestingly, disruption of the IL-13 gene, but not the IFN-gamma gene, prevented emphysema and pulmonary inflammation in Tg mice. Moreover, when IL-18 production was induced in lung tissues for 4 weeks through the use of a doxycycline-dependent surfactant protein C promoter, interstitial inflammation was induced.
  
  
  CONCLUSIONS
  Our results indicate that IL-18 and IL-13 may have an important role in the pathogenesis of COPD.
authors.affiliation: Department of Internal Medicine 1, Kurume University School of Medicine, Kurume, Japan. hoshino@med.kurume-u.ac.jp
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
authors.forename: Seiya
authors.initials: S
authors.lastname: Kato
authors.forename: Naoki
authors.initials: N
authors.lastname: Oka
authors.forename: Haruki
authors.initials: H
authors.lastname: Imaoka
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.forename: Satoko
authors.initials: S
authors.lastname: Takei
authors.forename: Yasuhiko
authors.initials: Y
authors.lastname: Kitasato
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
authors.forename: Kentaro
authors.initials: K
authors.lastname: Yamada
authors.forename: Howard A
authors.initials: HA
authors.lastname: Young
authors.forename: Hisamichi
authors.initials: H
authors.lastname: Aizawa
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D004646:Emphysema / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology*; D018793:Interleukin-13 / Q000276:immunology*; D020382:Interleukin-18 / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D011014:Pneumonia / Q000276:immunology / Q000473:pathology; D011650:Pulmonary Alveoli / Q000276:immunology / Q000473:pathology; D029424:Pulmonary Disease, Chronic Obstructive / Q000276:immunology* / Q000503:physiopathology
chemical_list: D018793:Interleukin-13; D020382:Interleukin-18