rhIGF-1/BP3 Preserves Lung Growth and Prevents Pulmonary Hypertension in Experimental BPD.

Antenatal factors, such as chorioamnionitis(CA) and preeclampsia(PE), and postnatal injury are associated with an increased risk for BPD and PH after preterm birth. IGF-1 is markedly decreased in normal preterm infants, but whether IGF-1 treatment can prevent BPD or PH is unknown.
To evaluate whether postnatal treatment with rhIGF-1/BP3 improves lung growth and prevents PH in 2 antenatal models of BPD induced by intra-amniotic exposure to ETX or sFlt-1 and in a postnatal model due to prolonged hyperoxia.
ETX or sFlt-1 were administered into the amniotic sac of pregnant rats at E20 to simulate antenatal models of CA and PE, respectively. Pups were delivered by c-section at E22 and treated with rhIGF-1/BP-3 (0.02-20 mg/kg/day, intraperitoneal) or buffer for 2 weeks. Study endpoints included radial alveolar counts(RAC), vessel density, and right ventricular hypertrophy(RVH). Direct effects of rhIGF-1/BP-3 (250 ng/ml) on fetal lung endothelial cell(LEC) proliferation and tube formation and alveolar type 2 cell(AT2C) proliferation were studied by standard methods in vitro.
Antenatal ETX and antenatal sFlt-1 reduced RAC and decreased RVH in infant rats. In both models, postnatal rhIGF-1/BP-3 treatment restored RAC and RVH to normal values when compared with placebo injections. rhIGF-1/BP3 treatment also preserved lung structure and prevented RVH after postnatal hyperoxia. In vitro studies showed that rhIGF-1/BP3 treatment increased LEC and AT2 cell proliferation.
Postnatal rhIGF-1/IGFBP-3 treatment preserved lung structure and prevented RVH in antenatal and postnatal BPD models. rhIGF-1/BP-3 treatment may provide a novel strategy for the prevention of BPD in preterms.