Research ArticleLUNG INJURY

Therapeutic exercise attenuates neutrophilic lung injury and skeletal muscle wasting

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Science Translational Medicine  11 Mar 2015:
Vol. 7, Issue 278, pp. 278ra32
DOI: 10.1126/scitranslmed.3010283

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Exercising away lung injury

The benefits of exercise for healthy people are undisputed, but recent evidence suggests that exercise may have its place even among the sickest patients in the intensive care unit. New findings by Files et al. help explain these observations by using mouse models to find a mechanistic link between exercise and benefits in the acute respiratory distress syndrome, which they also confirm in human patients with respiratory failure who receive therapeutic exercise. The benefits of exercise in this setting include attenuation of muscle wasting as well as decreased lung inflammation. Although these improvements are both linked to exercise, they occur by different mechanisms, suggesting potential future approaches for more directed therapeutic intervention.


Early mobilization of critically ill patients with the acute respiratory distress syndrome (ARDS) has emerged as a therapeutic strategy that improves patient outcomes, such as the duration of mechanical ventilation and muscle strength. Despite the apparent efficacy of early mobility programs, their use in clinical practice is limited outside of specialized centers and clinical trials. To evaluate the mechanisms underlying mobility therapy, we exercised acute lung injury (ALI) mice for 2 days after the instillation of lipopolysaccharides into their lungs. We found that a short duration of moderate intensity exercise in ALI mice attenuated muscle ring finger 1 (MuRF1)–mediated atrophy of the limb and respiratory muscles and improved limb muscle force generation. Exercise also limited the influx of neutrophils into the alveolar space through modulation of a coordinated systemic neutrophil chemokine response. Granulocyte colony-stimulating factor (G-CSF) concentrations were systemically reduced by exercise in ALI mice, and in vivo blockade of the G-CSF receptor recapitulated the lung exercise phenotype in ALI mice. Additionally, plasma G-CSF concentrations in humans with acute respiratory failure (ARF) undergoing early mobility therapy showed greater decrements over time compared to control ARF patients. Together, these data provide a mechanism whereby early mobility therapy attenuates muscle wasting and limits ongoing alveolar neutrophilia through modulation of systemic neutrophil chemokines in lung-injured mice and humans.

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