Elevated HSP27, HSP70 and HSP90 alpha in chronic obstructive pulmonary disease: markers for immune activation and tissue destruction.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of death. Although the underlying pathomechanism remains poorly understood, COPD is accompanied by increased cellular stress and inflammation. We investigated serum contents of heat shock proteins (HSP 27, 60, 70, 90 alpha), 20S proteasomes, C-reactive protein (CRP), and interleukin-6 (IL-6) in patients with mild or severe COPD, healthy smokers and nonsmokers. HSP27, HSP70 and HSP90 alpha were significantly altered in patients suffering from COPD as compared to controls. HSP27 and HSP70 are potential novel serum markers for the diagnosis of COPD in the smoking population. This is the first study to demonstrate elevated serum levels of the described heat shock proteins in patients with COPD. We showed sensitivity and specificity of serum HSP27 and HSP70 as diagnostic markers for COPD.

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 apoptosis. 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.