ELEVATED IL-6 IN MIDTRIMESTER AMNIOTIC-FLUID IS INVOLVED WITH THE ONSET OF PREECLAMPSIA

PROBLEM: The primary defect of placental development in preeclampsia i s speculated to occur at midtrimester gestation. Abnormal feto-materna l immune reactions have been considered as factors in such defective p lacentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens we re retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and ges tations measured for cytokines tumor necrosis factor-alpha (TNF-alpha) , interleukin (IL-1 beta, IL-6, and IL-8). The effect of each cytokine on thrombomodulin levels was tested in cultured trophoblast cells. RE SULTS: Among the measured cytokines, IL-6 and IL-8 were significantly elevated in the midtrimester amniotic fluid of the future preeclamptic group. Trophoblasts stimulated with TNF-alpha plus IL-6 had significa ntly decreased levels of cellular thrombomodulin compared to those wit hout cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimeste r amniotic fluid suggest an abnormal fetomaternal immune response occu rring before the clinical manifestation of preeclampsia. Cytokine-indu ced suppression of thrombomodulin in trophoblasts may be directly invo lved in the pathogenesis of preeclampsia.