G-CSF's Therapeutic Potential Explored in Premature Infants' Lung and Eye Health

Recent research published in The American Journal of Pathology has unveiled groundbreaking insights into the role of granulocyte colony-stimulating factor (G-CSF) in neonatal diseases affecting premature babies, specifically bronchopulmonary dysplasia (BPD) and retinopathy of prematurity (ROP).

Advancements in the care of premature infants have significantly improved survival rates. However, the rising incidence of lifelong conditions such as BPD and ROP poses ongoing challenges. BPD, characterized as chronic lung disease of immaturity, impacts approximately one-third of highly premature infants, causing enduring lung damage. It often co-occurs with ROP, a neonatal eye disease leading to irreversible vision impairment.

Lead investigator, Margaret L. Hibbs, Ph.D., from the Leukocyte Signalling Laboratory at Monash University, shares, "Our laboratory focuses on inflammation and its underlying mechanisms, and we have been studying myeloid colony-stimulating factors for many years. Previous work by us reported that G-CSF was pathogenic in chronic obstructive pulmonary disease (COPD), and this has now been shown by others to occur in asthma."

The study, utilizing a neonatal mouse model, revealed that G-CSF was significantly induced in response to hyperoxia, a condition associated with BPD. Preterm infants with severe BPD also exhibited increased plasma G-CSF levels.

Notably, neonatal mice deficient in G-CSF demonstrated reduced alveolar damage and protection against retinopathy when exposed to hyperoxia. Professor Hibbs highlights, "Our studies identify a new mechanism in BPD that is therapeutically tractable and may help rescue the lungs and sight of infants from life-long damage."

In response to a high oxygen insult, the lungs of wild-type mice (left-hand side) show alveolar simplification and enlargement, septal wall thickening (blue arrow), and leukocyte infiltration (black arrows), all features seen in human disease. Deficiency of granulocyte colony-stimulating factor (G-CSF) in mice (G-CSF-/-) markedly protects the lungs from these traits (right-hand side) Credit: The American Journal of Pathology

Co-investigator Evelyn Tsantikos, Ph.D., adds, "These studies produced some surprises, including the unexpected protection that G-CSF deficiency afforded to the endothelial compartment."

First author Lakshanie C. Wickramasinghe, Ph.D., emphasizes the collaborative nature of the research, involving clinical collaborators to gain a comprehensive understanding. Professor Hibbs concludes, "Our findings suggest that G-CSF is a pathological mechanism common to both [lung and eye diseases], which may advance a new therapeutic strategy to improve the care and long-term outcomes of these vulnerable premature infants."

These findings hold promise for developing targeted therapeutic interventions for neonatal diseases, potentially transforming the way premature infants are cared for and improving their long-term outcomes.

Reference

Lakshanie C. Wickramasinghe et al, Granulocyte Colony-Stimulating Factor is a Determinant of Severe Bronchopulmonary Dysplasia and Coincident Retinopathy, The American Journal of Pathology (2023). DOI: 10.1016/j.ajpath.2023.07.006