title: Time course of cigarette smoke-induced changes of systemic inflammation and muscle structure.
abstract: It has become more evident that long-term cigarette smoking (LTCS) has an important extrapulmonary toxicity. The aim of the study was to investigate the time-dependent effects of cigarette smoke exposure on exercise capacity, markers of systemic inflammation, and skeletal muscle structure. c57bl/6j-mice were either exposed to mainstream cigarette smoke for 6 h/day, 5 days/wk [smoke-exposed (SE) group] or assigned to the control, unexposed group (Con group). SE group mice were exposed for 8, 16, 24, and 32 wk to smoke and unexposed Con mice were used as age-matched controls. Exercise capacity was investigated by spiroergometry. Systemic inflammatory status was analyzed by flow cytometry and multiplexed fluorescent immunoassay. For analysis of muscle tissue, histological techniques and microarray analysis were used. Mice of the SE group exhibited a lower increase of body mass and a decrease of V̇o2 max (P < 0.05). An increase of lymphocyte CD62, ICAM, and VCAM expression was found in SE mice (P < 0.05). A biphasic trend of protein up- and downregulation was observed in markers of systemic inflammation, tissue deterioration, and allergic reactions such as C-reactive protein (CRP), eotaxin, haptoglobin, macrophage colony-stimulating factor-1 (M-CSF-1), and macrophage inflammatory protein-1γ (MIP-1γ). Thereby, the expression of several chemotactic proteins in plasma correlated with their expression in muscle. A time-dependent decrease of muscle mass, oxidative type-I fibers, and muscle cross-sectional area was found (P < 0.05). Microarray analysis revealed a SE-induced upregulation of several pathways of metabolic processes and tissue degradation. Taken together it was found that the loss of exercise capacity and systemic inflammation are early events of SE, which might induce muscular atrophy and loss of oxidative muscle capacity.
authors.affiliation: Department of Sports Medicine, Justus Liebig-University Giessen, Giessen, Germany; and karsten.krueger@sport.uni-giessen.de.
authors.forename: K
authors.initials: K
authors.lastname: Krüger
authors.affiliation: Department of Sports Medicine, Justus Liebig-University Giessen, Giessen, Germany; and.
authors.forename: G
authors.initials: G
authors.lastname: Dischereit
authors.affiliation: Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: M
authors.initials: M
authors.lastname: Seimetz
authors.affiliation: Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Wilhelm
authors.affiliation: Excellence Cluster Cardio-Pulmonary System, Universities of Giessen and Marburg Lung Center, Member of the German Center for Lung Research, Giessen, Germany.
authors.forename: N
authors.initials: N
authors.lastname: Weissmann
authors.affiliation: Department of Sports Medicine, Justus Liebig-University Giessen, Giessen, Germany; and.
authors.forename: F C
authors.initials: FC
authors.lastname: Mooren
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism*; D015992:Body Mass Index; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D004195:Disease Models, Animal; D020869:Gene Expression Profiling; D007249:Inflammation / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D009133:Muscular Atrophy / Q000139:chemically induced* / Q000378:metabolism / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D010101:Oxygen Consumption; D010805:Physical Conditioning, Animal; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012907:Smoking / Q000009:adverse effects*; D013997:Time Factors
chemical_list: D015415:Biomarkers; D016207:Cytokines; D012333:RNA, Messenger
keywords: COPD; cytokines; exercise capacity; lymphocytes; muscle wasting