A systems biology approach reveals a link between systemic cytokines and skeletal muscle energy metabolism in a rodent smoking model and human COPD

Peter K Davidsen, John M Herbert, Philipp Antczak, Kim Clarke, Elisabet Ferrer, Victor I Peinado, Constancio Gonzalez, Josep Roca, Stuart Egginton, Joan A Barberá, Francesco Falciani

A relatively large percentage of patients with chronic obstructive pulmonary disease (COPD) develop systemic co-morbidities that affect prognosis, among which muscle wasting is particularly debilitating. Despite significant research effort, the pathophysiology of this important extrapulmonary manifestation is still unclear. A key question that remains unanswered is to what extent systemic inflammatory mediators might play a role in this pathology. Cigarette smoke (CS) is the main risk factor for developing COPD and therefore animal models chronically exposed to CS have been proposed for mechanistic studies and biomarker discovery. Although mice have been successfully used as a pre-clinical in vivo model to study the pulmonary effects of acute and chronic CS exposure, data suggest that they may be inadequate models for studying the effects of CS on peripheral muscle function. In contrast, recent findings indicate that the guinea pig model (Cavia porcellus) may better mimic muscle wasting.