Increased Levels of IGF-1 and Beta2-Microglobulin in Epithelial Lining Fluid of Preterm Newborns Developing Chronic Lung Disease: Effects of rhG-CSF

Abstract

Insulin-like growth factor-1 (IGF-1) is involved in regulating the TH-l/TH-2 balance, favoring the development of the TH-2 compartment which enhances fibrosis, one of the main characteristics of Chronic Lung Disease (CLD) in premature newborns. Limited data is available concerning a possible association between early epithelial lining fluid (ELF) concentrations of IGF-1 (total and free forms), IGF-binding protein-3 (IGFBP-3), b2-microglobulin (B2M) and subsequent development of CLD in preterm neonates. If neutropenic, preterm neonates are frequently treated with recombinant human Granulocyte Colony Stimulating Factor (rhG-CSF). The objective of the study was to correlate ELF concentrations of IGF-1 and B2M during the first week of life both in non-neutropenic and in rhG-CSF-treated neutropenic preterm neonates, with subsequent development in CLD. Thirty preterm neonates with Respiratory Distress Syndrome (6 with neutropenia) were studied. Eleven out of 24 non-neutropenic preterm infants (46%) and all of the six neutropenic subjects (100%) developed CLD. With the exception of first day values, there was a clear similarity in the behaviors of assayed molecules between non-neutropenic and neutropenic patients developing CLD. Non-neutropenic patients without CLD showed significantly lower values of free IGF-1 and B2M both on days 1 and 3. Total IGF-I and cell counts were different only on the 3rd day. Conclusions: 1) the mechanisms leading to CLD might be mediated by high levels of IGF-family molecules soon after birth 2) B2M could be a marker of increased bronchoalveolar lavage fluid cellularity with potential inflammatory properties 3) G-CSF treatment induces an increased synthesis of IGF-1 molecules by cells recruited in the lung, with possible enhancement of the fibrogenic mechanisms.