Previous studies have shown that
chorioamnionitis, with increased
IL-6, promotes fetal lung maturation and decreases the incidence of
respiratory distress syndrome in premature neonates. However, the expression pattern and the effects of
IL-6 on fetal lung growth mechanisms remain unknown.
IL-6 expression was assessed by in situ hybridization and by real-time PCR between 14.5 and 21.5 d postconception. Normal and
nitrofen-induced hypoplastic lung explants were cultured with increasing
IL-6 doses or
IL-6 neutralizing antibodies. Branching, cellular proliferation (Ki-67) and MAPK phosphorylation in fetal lung explants were analyzed. Pulmonary primitive epithelium expressed
IL-6 constitutively throughout all gestational ages, displaying highest levels during earliest stages. In normal and hypoplastic lung explants,
IL-6 neutralizing antibodies significantly reduced, whereas
IL-6 supplementation induced a biphasic effect (lower doses increased, while the highest dose did not accomplish additional effect) on branching and cellular proliferation.
IL-6 enhanced p38-MAPK phosphorylation without changing MEK1/2 and JNK pathways. The present study suggests a physiological role for
IL-6 on pulmonary branching mechanisms most likely involving p38-MAPK intracellular signalling pathway.