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Effects of rehabilitative exercise on peripheral muscle TNF, IL-6, IGF-I and MyoD expression in patients with COPD

¹ National and Kapodistrian University of Athens, Department of Physical Education and Sport Science, Athens, Greece
² National and Kapodistrian University of Athens, Department of Critical Care Medicine and Pulmonary Services, Pulmonary Rehabilitation Centre, Evangelismos Hospital, G.P. Livanos and M. Simou Laboratories, Athens, Greece

Correspondence to:
Dr Ioannis Vogiatzis, National and Kapodistrian University of Athens – Thorax Foundation, 3 Ploutarhou Str 106 75, Athens, Greece; gianvog{at}phed.uoa.gr

Background: Skeletal muscle wasting commonly occurs in patients with chronic obstructive pulmonary disease (COPD) and has been associated with the presence of systemic inflammation. This study investigated whether rehabilitative exercise training decreases the levels of systemic or local muscle inflammation or reverses the abnormalities associated with muscle deconditioning.

Methods: Fifteen patients with COPD (mean (SE) forced expiratory volume in 1 s 36 (4)% predicted) undertook high-intensity exercise training 3 days/week for 10 weeks. Before and after the training programme the concentration of tumour necrosis factor (TNF), interleukin-6 (IL-6) and C-reactive protein (CRP) in plasma was determined by ELISA, and vastus lateralis mRNA expression of TNF, IL-6, total insulin-like growth factor-I (IGF-I) and its isoform mechanogrowth factor (MGF) and myogenic differentiation factor D (MyoD) were assessed by real-time PCR. Protein levels of TNF, IGF-I and MyoD were measured by Western blotting.

Results: Rehabilitation improved peak exercise work rate by 10 (2%) (p = 0.004) and mean fibre cross-sectional area from 4061 (254) µm² to 4581 (241) µm² (p = 0.001). Plasma inflammatory mediators and vastus lateralis expression of TNF and IL-6 were not significantly modified by training. In contrast, there was a significant increase in mRNA expression of IGF-I (by 67 (22)%; p = 0.044), MGF (by 67 (15)%; p = 0.002) and MyoD (by 116 (30)%; p = 0.001). The increase observed at the mRNA level was also seen at the protein level for IGF-I (by 72 (36)%; p = 0.046) and MyoD (by 67 (21)%; p = 0.012).

Conclusions: Pulmonary rehabilitation can induce peripheral muscle adaptations and modifications in factors regulating skeletal muscle hypertrophy and regeneration without decreasing the levels of systemic or local muscle inflammation.

Abbreviations: COPD, chronic obstructive pulmonary disease; CRP, C-reactive protein; FEV₁, forced expiratory volume in 1 s; FVC, forced vital capacity; GAPDH, glyceraldehyde-3-phosphate dehydrogenase; IGF-I, insulin-like growth factor-I; IL, interleukin; MGF, mechanogrowth factor; MyoD, myogenic differentiation factor D; TNF, tumour necrosis factor