Glucocorticoids and lung development in the fetus and preterm infant

During the final prenatal period of fetal lung development in humans, impor tant maturational processes occur, including the production of surfactant n ecessary to decrease surface tension at the air-liquid interface of the alv eoli. During early gestation, the glucocorticoid receptor is expressed in t he fetal lung, and glucocorticoids stimulate the production of surfactant-a ssociated proteins and increase phospholipid synthesis by enhancing the act ivity of phosphatidylcholine. Other glucocorticoid-induced effects may incl ude stimulation of cell maturation and differentiation, inhibition of DNA s ynthesis, changes in interstitial tissue components, stimulation of antioxi dant enzymes, and regulation of pulmonary fluid metabolism. Recently, it wa s suggested that glucocorticoids are also important in postnatal pulmonary development, and may be related to the development of neonatal lung disease in preterm infants. Surfactant deficiency that can be prevented by antenat al corticosteroid treatment causes infant respiratory distress syndrome and requires mechanical ventilation. Ventilation by itself or in combination w ith high revels of oxygen, fluid overload, pulmonary infections, sepsis, an d air leak syndrome causes an acute pulmonary inflammatory reaction that ma y result in chronic lung disease or bronchopulmonary dysplasia. Glucocortic oids are effective in the treatment of chronic lung disease of prematurity and regulate the inflammatory response by the interaction with transcriptio n factors such as nuclear factor kappaB and activated protein 1. Indeed, in flammatory cells and the levels of chemokines and cytokines in bronchoalveo lar fluid decrease after dexamethasone treatment. However, treatment of fet uses and preterm infants with repeated and/ or high doses of corticosteroid s may have considerable long-term side effects on somatic, brain, and lung growth. The difficult balance between short-term gain and the possible long -term side effects of glucocorticoids in preterms remains a difficult issue . (C) 2001 Wiley-Liss, Inc.