Transfer of Inflammatory Cytokines Across the Placenta

OBJECTIVE: The purpose of this study was to determine whether the placental transfer of interleukin (IL)-1alpha, IL-6, and tumor necrosis factor-alpha (TNF-alpha) occurs. METHODS: Four normal-term placentas were perfused for maternal-fetal transfer of the cytokines, 2 placentas for fetal-maternal transfer, and 4 additional placentas were used for an endogenous control. The ex vivo isolated cotyledon human placental perfusion model was used. The reference compound antipyrine was used to determine the transport fraction and clearance index of the cytokines. The cytokines were added to either the maternal or fetal circulations, and samples were collected for 1 hour in a constant-flow open circulation. Cytokine levels were compared between the study and control placentas. Concentrations of the cytokines were measured by sandwich enzyme immunoassay. RESULTS: The clearance index for the maternal-fetal transfer of IL-1alpha and TNF-alpha was 0.001, suggesting minimal transfer to the fetal circulation. The clearance index for IL-6 was 0.30, indicating transfer to the fetal circulation. When the cytokines were added to the fetal circulation, the clearance index for IL-1alpha was 0.001, again indicating minimal transfer. The clearance index for TNF-alpha in the fetal-maternal study was not determined. IL-6 had a clearance index of 0.23, which was similar to that observed with maternal-fetal transfer. IL-6 concentrations in the study placentas were higher than the concentrations found in the controls. CONCLUSION: There appears to be bidirectional transfer of IL-6 in the healthy-term human placental perfusion model. LEVEL OF EVIDENCE: II-2