title: Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD.
abstract: BACKGROUND
  Chronic obstructive pulmonary disease (COPD) is a worldwide burden and a major cause of death. The disease is accompanied by chronic inflammation and increased cellular turnover that is partly due to an overwhelming induction of apoptosis. In this study, we hypothesized that systemic markers of apoptosis are altered in patients with mild-to-severe COPD.
  
  
  METHODS
  A total number of 64 patients and controls were enrolled in the study. Lung function parameters of all groups (nonsmoker, healthy smoker, COPD GOLD I&II, COPD GOLD III&IV) were evaluated at the time of inclusion. Enzyme-linked immunosorbent assays were used to quantify protein levels in serum samples.
  
  
  RESULTS
  Serum contents of apoptotic end-products caspase-cleaved cytokeratin-18 and histone-associated-DNA-fragments were increased in patients with COPD, whereas anti-inflammatory soluble ST2 showed a peak in patients with COPD I&II (P=0.031) compared to healthy smokers. Levels of pro-inflammatory caspase-1/ ICE correlated significantly with the number of pack years (R=0.337; P=0.007).
  
  
  CONCLUSIONS
  Our results indicate a systemic release of apoptosis-specific proteins as markers for increased cellular turnover accompanied by progression of COPD. Furthermore, soluble ST2 seems to have a critical role in the anti-inflammatory regulatory mechanism at early stages of the disease.
authors.affiliation: Department of Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Stefan
authors.initials: S
authors.lastname: Hacker
authors.forename: Christopher
authors.initials: C
authors.lastname: Lambers
authors.forename: Andreas
authors.initials: A
authors.lastname: Pollreisz
authors.forename: Konrad
authors.initials: K
authors.lastname: Hoetzenecker
authors.forename: Michael
authors.initials: M
authors.lastname: Lichtenauer
authors.forename: Andreas
authors.initials: A
authors.lastname: Mangold
authors.forename: Tina
authors.initials: T
authors.lastname: Niederpold
authors.forename: Andreas
authors.initials: A
authors.lastname: Hacker
authors.forename: György
authors.initials: G
authors.lastname: Lang
authors.forename: Martin
authors.initials: M
authors.lastname: Dworschak
authors.forename: Thomas
authors.initials: T
authors.lastname: Vukovich
authors.forename: Christopher
authors.initials: C
authors.lastname: Gerner
authors.forename: Walter
authors.initials: W
authors.lastname: Klepetko
authors.forename: Hendrik Jan
authors.initials: HJ
authors.lastname: Ankersmit
mesh_terms: D017209:Apoptosis; D015415:Biomarkers / Q000097:blood; D020169:Caspases / Q000097:blood / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D003710:Demography; D005260:Female; D006657:Histones / Q000097:blood*; D006801:Humans; D000072179:Interleukin-1 Receptor-Like 1 Protein; D016753:Interleukin-10 / Q000097:blood; D053538:Keratin-18 / Q000097:blood*; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000097:blood* / Q000473:pathology*; D011956:Receptors, Cell Surface / Q000097:blood*; D012995:Solubility
chemical_list: D015415:Biomarkers; D006657:Histones; C079241:IL1RL1 protein, human; D000072179:Interleukin-1 Receptor-Like 1 Protein; D053538:Keratin-18; D011956:Receptors, Cell Surface; D016753:Interleukin-10; D004247:DNA; D020169:Caspases