Granulocyte colony-stimulating factor is a determinant of severe bronchopulmonary dysplasia and coincident retinopathy.

Bronchopulmonary dysplasia (BPD, also called chronic lung disease of immaturity) afflicts approximately one-third of all extremely premature infants causing lifelong lung damage. There is no effective treatment other than supportive care. Retinopathy of prematurity (ROP), which irreversibly impairs vision, is common in BPD, suggesting related pathogenesis, but specific mechanisms of BPD and ROP are obscure. A neonatal mouse hyperoxic model of coincident BPD and retinopathy was used to screen for candidate mediators, which revealed that granulocyte colony-stimulating factor (G-CSF/CSF3) was significantly upregulated in mouse lung lavage fluid and plasma at postnatal day 14 in response to hyperoxia. Preterm infants with more severe BPD had elevated plasma G-CSF. G-CSF-deficient neonatal pups showed significantly reduced alveolar simplification, normalised alveolar and airway resistance and normalised weight gain compared to wild type pups following hyperoxic lung injury. This was associated with a marked reduction in the intensity, and activation state, of neutrophilic and monocytic inflammation and its attendant oxidative stress response, and protection of lung endothelial cells. G-CSF deficiency also provided partial protection against ROP. The findings in this study implicate G-CSF as a pathogenic mediator of BPD and ROP and suggest the therapeutic utility of targeting G-CSF biology to treat these conditions. 199 words.