Transfer of proinflammatory cytokines across term placenta.
Increased concentrations of proinflammatory cytokines in amniotic fluid indicate the presence of intra-amniotic inflammation and increase the risk of preterm birth, cerebral palsy, and bronchopulmonary dysplasia. The purpose of this study was to find out if the proinflammatory cytokines, tumor necrosis factor alpha (TNF-alpha), interleukin (IL)-1beta, and IL-6, transfer across the placenta, and thereby determine whether intra-amniotic inflammatory response, measured from the amniotic fluid, is of maternal or fetal origin. Nineteen placentas from healthy women undergoing elective cesarean delivery at term with intact membranes and without labor, were dually perfused ex vivo in an open circulation system for either 30 minutes or 2 hours. Tumor necrosis factor-alpha, IL-1beta, and IL-6 were added to maternal or fetal circulation in a concentration usually found in chorioamnionitis. As a reference, placentas without added cytokine were also perfused. The concentrations of cytokines were determined by enzyme immunoassays (enzyme-linked immunosorbent assay [ELISA]). After the addition of the cytokine to the arterial perfusate, the venous concentration on the same side of the placenta increased rapidly and reached a plateau at 10 minutes. No transfer of any cytokine in either direction was detected. Some endogenous release of IL-6 was observed in response to the perfusion. Proinflammatory cytokines do not cross normal term placenta.