title: Interleukin-10 modulates pulmonary neutrophilic inflammation induced by cigarette smoke exposure.
abstract: OBJECTIVE
  Interleukin (IL)-10 is an anti-inflammatory cytokine, but its role in cigarette smoke (CS)-induced inflammation and chronic obstructive pulmonary disease (COPD) has not been fully elucidated. The purpose of this study was to investigate the effect of IL-10 deficiency on CS-induced pulmonary inflammation in mice in vivo and in vitro.
  
  
  METHODS
  IL-10-deficient and wild-type control mice with a C57BL6/J genetic background were exposed to CS, and inflammatory cells in bronchoalveolar lavage fluid (BALF) and mRNA of cytokines in lung were evaluated with enzyme-linked immunosorbent assay (ELISA) and reverse transcription polymerase chain reaction (RT-PCR).
  
  
  RESULTS
  During 12 days of daily CS exposure to wild-type mice, neutrophil counts in BAL fluid and tumor necrosis factor (TNF)-α mRNA expression were increased, peaked at day 8, and then declined on day 12 when the level of IL-10 reached its peak. In IL-10-deficient mice, neutrophil recruitment and TNF-α mRNA levels induced by CS exposure were significantly greater than those in wild-type mice. Keratinocyte-derived chemokine (KC; murine ortholog of human CXCL8) and granulocyte macrophage colony-stimulating factor (GM-CSF) mRNA levels or matrix metalloproteinase(MMP)-9 protein levels were not correlated with neutrophil count.
  
  
  CONCLUSIONS
  IL-10 had a modulatory effect on CS-induced pulmonary neutrophilic inflammation and TNF-α expression in mice in vivo and therefore appears to be an important endogenous suppressor of airway neutrophilic inflammation.
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Manabu
authors.initials: M
authors.lastname: Higaki
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.|b Department of Public Health, Graduate School of Medicine , Juntendo University , Tokyo , Japan.
authors.forename: Hiroo
authors.initials: H
authors.lastname: Wada
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Mikura
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Yasutake
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Masuo
authors.initials: M
authors.lastname: Nakamura
authors.affiliation: c Department of Infectious Diseases , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Mamoru
authors.initials: M
authors.lastname: Niikura
authors.affiliation: c Department of Infectious Diseases , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Fumie
authors.initials: F
authors.lastname: Kobayashi
authors.affiliation: d Department of Pathology , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kamma
authors.affiliation: c Department of Infectious Diseases , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Kamiya
authors.affiliation: e Airway Disease Section, National Heart and Lung Institute , Imperial College London , London , UK.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Ito
authors.affiliation: e Airway Disease Section, National Heart and Lung Institute , Imperial College London , London , UK.
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Barnes
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Goto
authors.affiliation: a Department of Respiratory Medicine , Kyorin University School of Medicine , Tokyo , Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Takizawa
mesh_terms: D000818:Animals; D016753:Interleukin-10 / Q000502:physiology*; D008070:Lipopolysaccharides / Q000633:toxicity; D017737:Macrophages, Peritoneal / Q000187:drug effects; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000032:analysis; D051379:Mice; D008810:Mice, Inbred C57BL; D020556:Neutrophil Infiltration; D011014:Pneumonia / Q000209:etiology* / Q000473:pathology; D012906:Smoke / Q000009:adverse effects*; D014026:Nicotiana / Q000009:adverse effects*
chemical_list: C556062:IL10 protein, mouse; D008070:Lipopolysaccharides; D012906:Smoke; D016753:Interleukin-10; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse
keywords: COPD; IL-10; matrix metalloproteinase-9; smoking; tumor necrosis factor-α