PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto-maternal immune reactions have been considered as factors in such defective placentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations 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. RESULTS: 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 significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.
PROBLEM: The primary defect of placental development in preeclampsia is speculated to occur at midtrimester gestation. Abnormal feto-maternal immune reactions have been considered as factors in such defective placentation. METHOD OF STUDY: Midtrimester amniotic fluid specimens were retrospectively identified as coming from gestations that later had severe preeclampsia develop, gestations with normal outcomes, and gestations 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. RESULTS: 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 significantly decreased levels of cellular thrombomodulin compared to those without cytokine addition. CONCLUSIONS: Elevated cytokines in midtrimester amniotic fluid suggest an abnormal fetomaternal immune response occurring before the clinical manifestation of preeclampsia. Cytokine-induced suppression of thrombomodulin in trophoblasts may be directly involved in the pathogenesis of preeclampsia.
Authors: Cissy Chenyi Zhou; Roxanna A Irani; Yingbo Dai; Sean C Blackwell; M John Hicks; Susan M Ramin; Rodney E Kellems; Yang Xia Journal: J Immunol Date: 2011-04-11 Impact factor: 5.422
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