Keratinocyte growth factor-2 intratracheal instillation significantly attenuates ventilator-induced lung injury in rats

Abstract

Preservation or restoration of normal alveolar epithelial barrier function is crucial for pulmonary oedema resolution. Keratinocyte growth factor-2 (KGF-2), a potent epithelial cell mitogen, may have a role in preventing ventilator-induced lung injury (VILI), which occurs frequently in mechanically ventilated patients. The aim of the study was to test the role of KGF-2 in VILI in rats. Forty healthy adult male Sprague-Dawley rats were randomly allocated into four groups, where rats in Groups HVZP (high-volume zero positive end-expiratory pressure) and HVZP+KGF-2 were given intratracheally equal PBS and 5 mg/kg KGF-2 72 hrs before 4 hrs HVZP ventilation (20 ml/kg), respectively, while PBS and KGF-2 were administered in the same manner in Groups Control and KGF-2, which underwent tracheotomy only with spontaneous breathing. Inflammatory cytokines (tumour necrosis factor-α, macrophage inflammatory protein 2), neutrophil and total protein levels in bronchoalveolar lavage fluid and surfactant protein mRNA expression in lung tissue were detected; the number of alveolar type II cells, lung water content and lung morphology were also evaluated. The results indicate that pre-treatment with KGF-2 showed dramatic improvement in lung oedema and inflammation compared with HVZP alone, together with increased surfactant protein mRNA and alveolar type II cells. Our results suggest that KGF-2 might be considered a promising prevention for human VILI or other acute lung injury diseases. © 2014 The Authors. Journal of Cellular and Molecular Medicine published by John Wiley & Sons Ltd and Foundation for Cellular and Molecular Medicine.