Pilot dose-ranging of rhIGF-1/rhIGFBP-3 in a preterm lamb model of evolving bronchopulmonary dysplasia

BACKGROUND: Low levels of insulin-like growth factor-1 (IGF-1) protein in preterm human infants are associated with bronchopulmonary dysplasia (BPD). We used our preterm lamb model of BPD to determine (1) dosage of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) to reach infant physiologic plasma levels; and (2) whether repletion of plasma IGF-1 improves pulmonary and cardiovascular outcomes. METHODS: Group 1: normal, unventilated lambs from 128 days gestation through postnatal age 5 months defined normal plasma levels of IGF-1. Group 2: continuous infusion of rhIGF-1/rhIGFBP-3 (0.5, 1.5, or 4.5 mg/kg/day; n = 2) for 3 days in mechanically ventilated (MV) preterm lambs determined that 1.5 mg/kg/day dosage attained physiologic plasma IGF-1 concentration of similar to 125 ng/mL, which was infused in four more MV preterm lambs. RESULTS: Group 1: plasma IGF-1 protein increased from similar to 75 ng/mL at 128 days gestation to similar to 220 ng/L at 5 months. Group 2: pilot study of the optimal dosage (1.5 mg/kg/day rhIGF-1/rhIGFBP-3) in six MV preterm lambs significantly improved some pulmonary and cardiovascular outcomes (p <0.1) compared to six MV preterm controls. RhIGF-1/rhIGFBP-3 was not toxic to the liver, kidneys, or lungs. CONCLUSIONS: Three days of continuous iv infusion of rhIGF-1/rhIGFBP-3 at 1.5 mg/kg/day improved some pulmonary and cardiovascular outcomes without toxicity.

Automated summary

This study used a preterm lamb model to investigate the effect of continuous infusion of recombinant human (rh) IGF-1 bound to binding protein-3 (IGFBP-3) on plasma IGF-1 levels and pulmonary and cardiovascular outcomes. The results showed that three days of continuous infusion of 1.5 mg/kg/day of rhIGF-1/rhIGFBP-3 improved some pulmonary and cardiovascular outcomes without toxicity.