Inflammatory Cytokines and Repair Factors in the Intercostal Muscles of Patients With Severe COPD

a b s t r a c t Objective: There is disagreement regarding the local action of cytokines in the respiratory muscles of patients with chronic obstructive pulmonary disease (COPD). The objective of this study was to analyze the relationships between cytokine expression and genetic activation of the mechanisms of muscle repair. Patients and Methods: Twenty-five patients with severe COPD and in stable condition were enrolled in the study. We performed a biopsy of the external intercostal muscle of the patients and analyzed the specimen for signs of muscle lesion (morphometry), infiltration of inflammatory cells (immunohistochemistry), and expression of selected genes (real-time polymerase chain reaction technique) corresponding to the cytokines (tumor necrosis factor α (TNF-α) and its type 1 and 2 receptors (TNFR1 and TNFR2), and interleukin (IL) 1β, IL-6, and IL-10), a pan-leukocyte marker (CD18), and key molecules in the repair- myogenesis pathways (Pax7, M-cadherin, and MyoD). Results: Expression of TNFR2 is directly related to inspiratory muscle function (represented by maximum sustainable inspiratory pressure; r=0.496; P<.05), whereas expression of CD18 is inversely related (r=0.462; P<.05). Moreover, expression of the 2 TNF-α receptors was directly related to that of the key molecules of the repair pathways analyzed (TNFR1 to Pax7 (r=0.650; P<.001) and M-cadherin (r=0.678; P<.001); TNFR2 to Pax7 (r=0.395; P<.05), M-cadherin (r=0.409; P<.05), and MyoD (r=0.418; P<.05)). Conclusions: Expression of TNF-α receptors bears a close relationship both to activation of the myogenesis programs and to inspiratory muscle function. This reinforces our hypothesis that some local cytokines take part in the repair of respiratory muscles in patients with COPD.