Novel Anti-Inflammatory Approaches for Currently Untreatable Diseases of the Preterm Baby

The severe chronic lung disease bronchopulmonary dysplasia (BPD) causes considerable suffering for premature infants and their families and contributes substantially to health care costs. Necrotising enterocolitis (NEC) is a disease of the premature gut that is poorly understood and carries a high mortality. No effective therapy is known for either devastating disease. In view of the importance of inflammation for BPD and NEC, we will assess how effectively two innovative anti-inflammatory mediators, interleukin 1 receptor antagonist (IL-1Ra) and IL-37, protect against BPD and NEC. In newborn mice with a BPD-like lung disease, we will quantify whether increased levels of IL-1Ra or IL-37 protect against the development of lung pathology as reflected in biochemical and cellular markers of inflammation and loss of alveolarisation and vascularisation on day 3 and 28 of life. In a newborn mouse model of NEC, involving formula feeding for 3 days and brief exposure to cold and hypoxia, we will assess the protective properties of IL-1Ra and IL-37 by histology and flow cytometry and by analysis of selected biochemical markers.