Hypoperfusion causes increased production of interleukin 6 and tumor necrosis factor alpha in the isolated, dually perfused placental cotyledon

OBJECTIVE: Our purpose was to determine whether exposure of the isolated, p erfused human placental cotyledon to different fetal circuit perfusion rate s, and to concomitant pressure differences, alters placental production of interleukin 6 and tumor necrosis factor alpha. STUDY DESIGN: The maternal and fetal circulations of 2 cotyledons from 5 pl acentas were perfused for 4 hours. The fetal circulation of 1 cotyledon was perfused at a low rate of 1 mL/min, and the other at a high rate of 10 mL/ min. The maternal circulation of each cotyledon was perfused at 10 mL/min. Effluents from the fetal circulation were collected at hourly intervals, an d concentrations of interleukin 6 and tumor necrosis factor alpha were dete rmined by enzyme-linked immunosorbent assay. Concentrations of interleukin 6, obtained from a prior study with an estimated physiologic fetal circulat ion rate of 4 mL/min, were compared with the low and high perfusion rate re sults. RESULTS: Concentrations of interleukin 6 and tumor necrosis factor alpha we re greater at the perfusion rate of 1 mL/min, in comparison with the perfus ion rate of 10 mL/min, with statistically significant differences achieved at 2 and 4 hours for interleukin 6 and at 4 hours for tumor necrosis factor alpha. Concentrations of both cytokines increased exponentially with time. Placental perfusion pressures were significantly greater at the perfusion rate of 10 mL/min. CONCLUSION: Placental hypoperfusion results in an increased production of b oth interleukin 6 and tumor necrosis factor alpha. This finding links place ntal perfusion abnormalities to the myriad of disorders associated with ele vated concentrations of inflammatory cytokines, including cerebral palsy.