-We tested the hypothesis that oxytocin-induced labor augmented IL-1-induced/ -stimulated lung fluid absorption in preterm guinea pig fetuses. IL-1 was administered subcutaneously daily to timed-pregnant guinea pigs for 3 days with and without simultaneous cortisol synthesis inhibition by metyrapone. At day 3, oxytocin was administered, and fetuses were delivered by abdominal hysterotomy at 61 and by oxytocin-induced birth at 68 days gestation. Delivered fetuses were instilled with isosmolar 5% albumin into the lungs, and lung fluid movement was measured over 1 h by mass balance. Lung fluid absorption was induced in 61-day and stimulated in 68-day gestation lungs by IL-1. Labor induction by oxytocin augmented IL-1-induced/-stimulated lung fluid absorption. Metyrapone pretreatment did not affect oxytocin-induced/-stimulated lung fluid absorption, while completely blocking IL-1-induced/-stimulated fluid absorption. Fetal lung fluid absorption, when present, was always propranolol and amiloride sensitive, suggesting that -adrenoceptor stimulation and amiloridesensitive sodium channels were critical for fluid absorption. Epithelial sodium channel and Na-K-ATPase subunit expressions were both increased by IL-1, but not further by oxytocin. Our results indicate that IL-1 release into the maternal blood circulation positively affects lung maturation due to the IL-1-induced release of cortisol and thus prepares the lungs for the epinephrine surge associated with labor.-adrenoceptors; cortisol; epinephrine; prenatal lung development; sodium transport CYTOKINES, SUCH AS INTERLEUKIN-1 (IL-1), can be important during pregnancy, because IL-1 has been detected in the placenta and amniotic fluid (12,44). In this regard, interleukins have been proposed as a signal for parturition onset, as cytokines can stimulate prostaglandin biosynthesis (41). During normal pregnancies, IL-1 is present in the amniotic fluid in low concentrations, but during preterm labor much higher amniotic fluid IL-1 concentrations are present (44). Intrauterine infection/inflammation may further elevate cytokine levels, the highest activity being attributable to IL-1 (44). Many prematurely born infants suffer from fetal infection and/or respiratory distress syndrome (RDS), both of which are important reasons for mortality of premature babies. Recent human data suggest that ion transport abnormalities across lung epithelial cells, i.e., an incomplete transition of lung fluid secretion to lung fluid absorption, can contribute to RDS development (1). Factors accelerating ion transport across alveolar cells may thus have benefits for the resolution of RDS. Recent experimental data have suggested that proinflammatory cytokines could also promote lung maturation (9,14,26,47). IL-1␣ increased mRNA surfactant protein expression and improved lung compliance in fetal rabbits (9). IL-1␣ also improved postnatal lung function with increased surfactant pool size without eliciting systemic inflammatory responses in lambs (14, 47). We recently reported that IL-...