Cytokines and production of surfactant components

The production of pulmonary surfactant, a complex of lipids and proteins that reduces surface tension at the alveolar air-liquid interface, is developmentally regulated. Several hormones, most notably glucocorticoids, are known to accelerate maturation of the surfactant system. Cytokines are polypeptides that act mostly in a paracrine fashion and possess a wide spectrum of activities on multiple types of cells. Many cytokines are produced by different lung cells at various stages of fetal development or under pathological conditions affecting the fetus. In addition, cytokines present in amniotic fluid or in the blood stream may reach the fetal lungs. Some cytokines, including epidermal growth factor, transforming growth factor-α, and interferon-γ have been shown to stimulate the production of surfactant components. On the other hand, tumor necrosis factor and transforming growth factor-β downregulate the production of surfactant lipids and proteins. We have recently shown that the proinflammatory cytokine interleukin-1 (IL-1) enhances the expression of surfactant protein A (SP-A) in fetal rabbit lung explants. In addition, injection of IL-1 into the amniotic fluid of fetal rabbits enhances the expression of surfactant proteins and improves the lung compliance of preterm animals. Preterm delivery is often associated with subclinical intraamniotic infection. In these cases, amniotic fluid concentrations of IL-1 are often elevated. We propose that this cytokine accelerates maturation of the surfactant system in fetal lungs and thus prepares the fetus for extrauterine life.