Increased soluble serum markers caspase-cleaved cytokeratin-18, histones, and ST2 indicate apoptotic turnover and chronic immune response in COPD.
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.
Hacker
Stefan
S
Department of Surgery, Medical University of Vienna, Vienna, Austria.
Lambers
Christopher
C
Pollreisz
Andreas
A
Hoetzenecker
Konrad
K
Lichtenauer
Michael
M
Mangold
Andreas
A
Niederpold
Tina
T
Hacker
Andreas
A
Lang
György
G
Dworschak
Martin
M
Vukovich
Thomas
T
Gerner
Christopher
C
Klepetko
Walter
W
Ankersmit
Hendrik Jan
HJ
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
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