CYTOKINE PROFILE IN QUADRICEPS MUSCLES OF PATIENTS WITH SEVERE CHRONIC OBSTRUCTIVE PULMONARY DISEASE

ROS, reactive oxygen species; NADPH, nicotinamide adenine dinucleotide phosphate. ABSTRACT Background: Systemic proinflammatory cytokines and oxidative stress have been described in association with peripheral muscle wasting and weakness of patients with severe chronic obstructive pulmonary disease (COPD), but their expression in skeletal muscle is unknown. Objectives of the present study were to determine muscle protein levels of selected cytokines in patients with COPD and to study their relationships with protein carbonylation as a marker of oxidative stress, quadriceps function, and exercise capacity. Methods: We conducted a cross-sectional study in which 36 cytokines were detected using a human antibody array in quadriceps specimens obtained from 19 patients with severe COPD and 7 healthy controls. Subsequently, selected cytokines [tumor necrosis factor (TNF)-alpha, TNF-alpha receptors I and II, interleukin (IL)-6, interferon-gamma, transforming growth factor (TGF)-beta, and vascular endothelial growth factor (VEGF)], as well as protein carbonylation (oxidative stress index) were determined using enzyme-linked immunosorbent assay (ELISA) in all muscles. Results: As compared to controls, vastus lateralis of COPD patients showed significantly lower protein ELISA levels of TNF-alpha, which positively correlated with their quadriceps function, TNF-alpha receptor II, and VEGF. Protein ELISA levels of IL-6, interferon-gamma, and TGF-beta did not differ between patients and controls. Quadriceps protein carbonylation was greater in the patients and inversely correlated with quadriceps strength amongst them. Conclusions: These findings do not support the presence of a pro-inflammatory environment within the quadriceps muscles of clinically and weight stable patients with severe COPD, despite evidence for increased oxidative stress and the presence of muscle weakness.