Abstract
The aim of this study was to test the hypothesis that systemic inflammation in patients with chronic obstructive pulmonary disease (COPD) is accompanied by enhanced interleukin 18 (IL-18) expression in skeletal muscle, which may precede muscle weight loss. Twenty patients with moderate to severe COPD [12 women, 66 ± 9.4 years of age and forced expiratory volume in 1 second (FEV1) of 32% ± 12 % of predicted value] and 20 healthy age-, gender-, and body mass index (BMI)-matched controls (10 nonsymptomatic smokers and 10 nonsmokers) were included in the study. Plasma levels of IL-18 were elevated in COPD patients (n = 20) versus healthy controls (n = 20) (221.2 pg/ml [196.0–294.2 pg/pl] vs. 164.8 pg/ml [144.4–193.3 pg/pl], p = 0.04) and IL-18 was expressed in skeletal muscle, with IL-18 mRNA levels being elevated in biopsies from COPD patients (n = 19) versus healthy controls (n = 18) (4.3 [2.6–5.9] vs. 2.4 [1.6–3.1], p = 0.003). Immunohistochemical evaluation revealed a strong expression of IL-18 in Type II muscle fibers from COPD patients. Plasma levels and skeletal muscle mRNA levels of tumor necrosis factor α (TNF-α) and IL-6 did not differ between the groups. Elevated skeletal muscle expression of IL-18 was found in COPD patients with normal body weight, indicating that IL-18 potentially may be involved in the pathogenesis of COPD-associated muscle wasting.
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Acknowledgments
The authors thank the subjects for their participation. Aase Vinum, Inger Schønheyder, Ruth Rousing, and Hanne Villumsen are acknowledged for their technical assistance. This work was supported by The Centre of Inflammation and Metabolism (supported by a grant from the Danish National Research Foundation, DG 02-512-555); The Copenhagen Muscle Research Centre (supported by grants from The University of Copenhagen, The Faculties of Science and of Health Sciences at this univesity); The Copenhagen Hospital Corporation; The Danish National Research Foundation (Grant 504-14); and the Commission of the European Communities (contract no. LSHM-CT-2004-005272 EXGENESIS). The study was also supported by grants from Danish Medical Research Council (No. 22-01-009), The Farmacist Foundation of 1991, Danish Lung Association, The Legacy of Ebba Celinder, and The Foundation of Managing Director Jacob Madsen & Spouse Olga Madsen.
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An erratum to this article can be found at http://dx.doi.org/10.1007/s00408-011-9330-3
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Petersen, A.M.W., Penkowa, M., Iversen, M. et al. Elevated Levels of IL-18 in Plasma and Skeletal Muscle in Chronic Obstructive Pulmonary Disease. Lung 185, 161–171 (2007). https://doi.org/10.1007/s00408-007-9000-7
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DOI: https://doi.org/10.1007/s00408-007-9000-7