Interleukin‐6 has a role in normal and hypoplastic fetal lung branching

Abstract

Introduction Several studies have shown that conditions that increase interleukin-6 (IL6) concentration, such as chorioamnionitis, improve lung volume and compliance as well as promote fetal lung maturation. However, the pattern of constitutive gene expression of IL6 as well as its effects is largely unknown during antenatal lung development. Aim We characterized IL6 expression during antenatal lung development and evaluated the effect of IL6 administration to normal and hypoplastic fetal lung explants. Methods In normal fetal lungs, IL6 expression was evaluated by in toto (15 days post-conception, dpc) and in situ hybridization (16, 18, 20 and 22 dpc), and relative quantifications were performed by realtime-PCR (β-actin as normalize gene). Additionally, normal and nitrofen-induced hypoplastic lungs (14 dpc) were cultivated with different concentrations of IL6 (0.01, 0.1, 1, 10, 100 ng/mL) during 4 days. We evaluated total bud count and epithelial perimeter that were compared with control conditions. Results IL6 was expressed by primitive lung epithelium during all studied gestational ages reaching maximal levels during pseudoglandular phase (16 dpc: 0.24±0.02; 18 dpc: 0.15±0.04; 20 dpc: 0.16±0.04; 22 dpc 0.05±0.02. p<0.05). Normal and hypoplastic lung explants cultivated with IL6 significantly increased the total bud count and epithelial perimeter in a dose-dependent manner. Conclusion The constitutive epithelial expression of IL6 during normal lung development and its stimulation of branching of normal and hypoplastic lung explants suggest a role for IL6 in fetal lung branching.