Increased Soluble Serum Markers Caspase-Cleaved Cytokeratin-18, Histones, and ST2 Indicate Apoptotic Turnover and Chronic Immune Response in COPD

Introduction: 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 apoplosis. In this study, we hypothesized that systemic markers of apoptosis are altered in patients with mild-to-severe COPD. Materials and 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). Discussion: 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. J. Clin. Lab. Anal. 23:372-379, 2009. (C) 2009 Wiley-Liss, Inc.