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Recombinant human insulin-like growth factor 1 complex preserves lung development in mechanically ventilated preterm
Kurt H Albertine1, Andrew Rebentisch1, Elaine Dawson1
1Division of Neonatology, Department of Pediatrics, University of Utah, Salt Lake City, UT, United States.
Insights
Recombinant human insulin-like growth factor-1 (rhIGF-1) complex improved lung development in preterm lambs. This therapy may reduce the risk of bronchopulmonary dysplasia in premature infants.
Area of Science:
- Neonatal medicine
- Pulmonary medicine
- Developmental biology
Background:
- Bronchopulmonary dysplasia is linked to low insulin-like growth factor-1 (IGF-1) in preterm infants.
- Postnatal IGF-1 replenishment is a potential strategy to prevent lung injury in premature neonates.
- Previous studies showed rhIGF-1 complex improved outcomes in preterm lambs.
Purpose of the Study:
- To assess the efficacy of a longer treatment period (7 days) with rhIGF-1 complex in younger preterm lambs.
- To evaluate the preservation of respiratory gas exchange, lung structure, and mechanics.
- To determine the safety and effectiveness of rhIGF-1 complex for lung maturation.
Main Methods:
- Mechanically ventilated preterm lambs (128d gestation) received continuous intravenous infusion of rhIGF-1 complex or saline for 7 days.
- Lambs were randomized into treatment and control groups (10 per group).
- Respiratory gas exchange, lung structure, and VEGF-R2 mRNA expression were assessed.
Main Results:
- RhIGF-1 complex significantly enhanced respiratory gas exchange and alveolar development.
- Improved alveolar capillary growth and VEGF-R2 mRNA expression were observed.
- No adverse effects on liver or kidney function were detected.
Conclusions:
- RhIGF-1 complex demonstrates potential as a safe and effective therapy for promoting lung maturation in preterm infants.
- This treatment may reduce the incidence and severity of bronchopulmonary dysplasia.
- Further research is warranted to confirm these findings in clinical settings.
Rationale:
Bronchopulmonary dysplasia is associated with low concentrations of insulin-like growth factor 1 (IGF-1) protein in preterm infants. Postnatal replenishment of IGF-1 protein is a potential approach to prevent the decline in preterm human infants. Our recent 3-day pilot study in mechanically ventilated preterm lambs (131 days' gestation; n = 6) demonstrated downstream signaling of human IGF-1 in sheep cells in vitro and that 1.5 mg/kg/d of recombinant human (rh) IGF-1 bound to binding protein 3 (IGFBP3; rhIGF-1 complex) delivered by continuous intravenous infusion provided physiological replacement of IGF-1 protein in plasma and suggested better pulmonary outcomes.
Objective:
This study assessed a longer period (7 days) of continuous treatment and larger sample size (10/group), using younger mechanically ventilated preterm lambs (128 days' gestation; equivalent to human lung development at ∼28 weeks' gestation) to allow evidence of preservation of respiratory gas exchange, alveolar formation and capillary growth, lung mechanics, and terminal bronchiole smooth muscle abundance.
Methods:
Preterm lambs were mechanically ventilated for 7 days. Lambs were randomized to blinded treatment with continuous intravenous infusion of either saline (vehicle control; 5 female/5 male) or rhIGF-1 complex (5 female/5 male), starting at 6 hours after operative delivery.
Measurements And Main Results:
RhIGF-1 complex significantly improved indices of respiratory gas exchange, alveolar formation, alveolar capillary growth, and VEGF-R2 messenger RNA expression, without adverse effects on liver or kidney function.
Conclusions:
RhIGF-1 complex may be an effective and safe therapy to promote functional and structural development underlying lung maturation in preterm infants and reduce the risk of developing bronchopulmonary dysplasia.
