Recovery of pulmonary structure and exercise capacity by treatment with granulocyte-colony stimulating factor (G-CSF) in a mouse model of emphysema.

Emphysema is a chronic obstructive pulmonary disease characterized abnormal dilatation of alveolar spaces, which impairs alveolar gas exchange, compromising the physical capacity of a patient due to airflow limitations. Here we tested the effects of G-CSF administration in pulmonary tissue and exercise capacity in emphysematous mice. C57Bl/6 female mice were treated with elastase intratracheally to induce emphysema. Their exercise capacities were evaluated in a treadmill. Lung histological sections were prepared to evaluate mean linear intercept measurement. Emphysematous mice were treated with G-CSF (3 cycles of 200 mg/kg/day for 5 consecutive days, with 7-day intervals) or saline and submitted to a third evaluation 8 weeks after treatment. Values of run distance and linear intercept measurement were expressed as mean SD and compared applying a paired t-test. Effects of treatment on these parameters were analyzed applying a Repeated Measures ANOVA, followed by Tukey’s post hoc analysis. p < 0.05 was considered statistically significant. Twenty eight days later, animals ran significantly less in a treadmill compared to normal mice (549.7 181.2 m and 821.7 131.3 m, respectively; p < 0.01). Treatment with G-CSF significantly increased the exercise capacity of emphysematous mice (719.6 200.5 m), whereas saline treatment had no effect on distance run (595.8 178.5 m). The PCR cytokines genes analysis did not detect difference between experimental groups. Morphometric analyses in the lung showed that saline-treated mice had a mean linear intercept significantly higher (p < 0.01) when compared to mice treated with G-CSF, which did not significantly differ from that of normal mice. Treatment with G-CSF promoted the recovery of exercise capacity and regeneration of alveolar structural alterations in emphysematous mice.