BPD is a common lung disease of premature infants, with devastating short- and long-term consequences. The pathogenesis of BPD is multi-factorial, but all triggers cause pulmonary inflammation. No therapy exists; thus, we investigated whether the anti-inflammatory IL-1Ra prevents murine BPD.

We precipitated BPD by perinatal inflammation (LPS injection to pregnant dams) and rearing pups in hyperoxia (65% or 85% O₂). Pups were treated daily with IL-1Ra or vehicle.

Vehicle-injected animals in both levels of hyperoxia developed a severe BPD-like lung disease (alveolar number and gas exchange area decreased by 60%, alveolar size increased 4-fold). IL-1Ra prevented this structural disintegration at 65%, but not 85% O₂. Hyperoxia depleted pulmonary immune cells by 67%; however, extant macrophages and dendritic cells were hyper-activated, with CD11b and GR1 highly expressed. IL-1Ra partially rescued the immune cell population in hyperoxia (doubling viable cells), reduced the percentage that were activated by 63%, and abolished the unexpected persistence of IL-1alpha and IL-1beta on d28 in hyperoxia/vehicle-treated lungs. On d3, perinatal inflammation and hyperoxia each triggered a distinct pulmonary immune response, with some pro-inflammatory mediators increasing 20-fold and some amenable to partial or complete reversal with IL-1Ra.

In summary, our analysis reveals a pivotal role for IL-1 in murine BPD and an involvement for MIP-1 and TREM-1. Because it effectively shields newborn mice from BPD, IL-1Ra emerges as a promising treatment for a currently irremediable disease that may potentially brighten the prognosis of the tiny preterm patients.