Elevated levels of IL-6 and IGFBP-1 predict low serum IGF-1 levels during continuous infusion of rhIGF-1/rhIGFBP-3 in extremely preterm infants
Susanna Klevebro, Gunnel Hellgren, Ingrid Hansen-Pupp, Dirk Wackernagel, Boubou Hallberg, Jan Borg, Aldina Pivodic, Lois Smith, David Ley, Ann Hellström, Susanna Klevebro, Gunnel Hellgren, Ingrid Hansen-Pupp, Dirk Wackernagel, Boubou Hallberg, Jan Borg, Aldina Pivodic, Lois Smith, David Ley, Ann Hellström
Abstract
Objective: Steady state insulin-like growth factor-1 (IGF-1) levels vary significantly during continuous intravenous infusion of recombinant human insulin-like growth factor-1/recombinant human insulin-like growth factor binding protein-3 (rhIGF-1/rhIGFBP-3) in the first weeks of life in extremely preterm infants. We evaluated interleukin-6 (IL-6) and insulin-like growth factor binding protein-1 (IGFBP-1) levels as predictors of low IGF-1 levels.
Methods: Nineteen extremely preterm infants were enrolled in a trial, 9 received rhIGF-1/rhIGFBP-3 and 10 received standard neonatal care. Blood samples were analyzed daily for IGF-1, IL-6 and IGFBP-1 during intervention with rhIGF-1/rhIGFBP-3.
Results: Thirty seven percent of IGF-1 values during active treatment were <20 μg/L. Among treated infants, higher levels of IL-6, one and two days before sampled IGF-1, were associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.30 (95% CI 1.03-1.63), p = .026, and 1.57 (95% CI 1.26-1.97), p < .001 respectively. Higher levels of IGFBP-1 one day before sampled IGF-1 was also associated with IGF-1 < 20 μg/L, gestational age adjusted OR 1.74 (95% CI 1.19-2.53), p = .004.
Conclusion: In preterm infants receiving continuous infusion of rhIGF-1/rhIGFBP-3, higher levels of IL-6 and IGFBP-1 preceded lower levels of circulating IGF-1. These findings demonstrate a need to further evaluate if inflammation and/or infection suppress serum IGF-1 levels. The trial is registered at ClinicalTrials.gov (NCT01096784).
Keywords: IGF-1; IGFBP-1; IL-6; Inflammation; Preterm infants; rhIGF-1/rhIGFBP-3.
Conflict of interest statement
Declaration of Competing Interest IH-P, DL and AH hold stock/stock options in Premalux AB, and have received consulting fees from Shire PLC. BH has received consulting fees from Premacure AB and Shire PLC, and grant/research support from Baxter. JB holds stock in Premalux AB.
Copyright © 2019 The Authors. Published by Elsevier Ltd.. All rights reserved.
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Source: PubMed