title: Responsiveness of blood and sputum inflammatory cells in Japanese COPD patients, non-COPD smoking controls, and non-COPD nonsmoking controls.
abstract: OBJECTIVE
  To compare pulmonary and systemic inflammatory mediator release, pre- and poststimulation, ex vivo, in cells from Japanese patients with chronic obstructive pulmonary disease (COPD), non-COPD smoking controls, and non-COPD nonsmoking controls (NSC).
  
  
  METHODS
  This was a nontreatment study with ten subjects per group. Inflammatory biomarker release, including interleukin (IL)-6 and -8, matrix metalloproteinase-9, and tumor necrosis factor (TNF)-α, was measured in peripheral blood mononuclear cells (PBMC) and sputum cells with and without lipopolysaccharide or TNF-α stimulation.
  
  
  RESULTS
  In PBMC, basal TNF-α release (mean ± standard deviation) was significantly different between COPD (81.6±111.4 pg/mL) and nonsmoking controls (9.5±5.2 pg/mL) (P<0.05). No other significant differences were observed. Poststimulation biomarker release tended to increase, with the greatest changes in the COPD group. The greatest mean increases were seen in the lipopolysaccharide-induced release of matrix metalloproteinase-9, TNF-α, and IL-6 from PBMC. Pre- and poststimulation data from sputum samples were more variable and less conclusive than from PBMC. In the COPD group, induced sputum neutrophil levels were higher and macrophage levels were lower than in either control group. Significant correlations were seen between the number of sputum cells (macrophages and neutrophils) and biomarker levels (IL-8, IL-6, and TNF-α).
  
  
  CONCLUSIONS
  This was the first study to compare cellular inflammatory mediator release before and after stimulation among Japanese COPD, smoking controls, and nonsmoking controls populations. Poststimulation levels tended to be higher in patients with COPD. The results suggest that PBMC are already preactivated in the circulation in COPD patients. This provides further evidence that COPD is a multicomponent disease, involving both airway and systemic inflammation.
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tomotaka
authors.initials: T
authors.lastname: Kawayama
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kinoshita
authors.affiliation: Department of Respiratory Medicine, Fukuoka Sanno Hospital, Fukuoka, Japan.
authors.forename: Kazuko
authors.initials: K
authors.lastname: Matsunaga
authors.affiliation: Biomedical Data Science Department, GlaxoSmithKline, Shibuya-ku, Tokyo, Japan.
authors.forename: Akihiro
authors.initials: A
authors.lastname: Kobayashi
authors.affiliation: Medical Affairs Respiratory Department, GlaxoSmithKline, Shibuya-ku, Tokyo, Japan.
authors.forename: Tomoyuki
authors.initials: T
authors.lastname: Hayamizu
authors.affiliation: Respiratory Global Franchise, GlaxoSmithKline, Uxbridge, UK.
authors.forename: Malcolm
authors.initials: M
authors.lastname: Johnson
authors.affiliation: Division of Respirology, Neurology, and Rheumatology, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Tomoaki
authors.initials: T
authors.lastname: Hoshino
mesh_terms: D000368:Aged; D015415:Biomarkers / Q000378:metabolism*; D002478:Cells, Cultured; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D007958:Leukocyte Count; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008875:Middle Aged; D009504:Neutrophils; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D012907:Smoking / Q000097:blood / Q000473:pathology / Q000503:physiopathology; D013183:Sputum / Q000166:cytology / Q000378:metabolism; D013223:Statistics as Topic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D020780:Matrix Metalloproteinase 9
keywords: chronic obstructive pulmonary disease; lipopolysaccharide; peripheral blood mononuclear cells; sputum; tumor necrosis factor-α