Elevated IL-6 in midtrimester amniotic fluid is involved with the onset of preeclampsia.
OBJECTIVE
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.


METHODS
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.
Nakabayashi
M
M
Tokyo Women's Medical College, Department of Obstetrics and Gynecology, Japan.
Sakura
M
M
Takeda
Y
Y
Sato
K
K
D000649:Amniocentesis; D000653:Amniotic Fluid / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism / Q000494:pharmacology; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005865:Gestational Age; D006801:Humans; D007231:Infant, Newborn; D015850:Interleukin-6 / Q000378:metabolism* / Q000494:pharmacology; D008423:Maternal Age; D011225:Pre-Eclampsia / Q000209:etiology*; D011247:Pregnancy; D011256:Pregnancy Outcome; D011262:Pregnancy Trimester, Second; D011446:Prospective Studies; D018180:Thrombomodulin / Q000378:metabolism; D014327:Trophoblasts / Q000276:immunology; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology
D016207:Cytokines; D015850:Interleukin-6; D018180:Thrombomodulin; D014409:Tumor Necrosis Factor-alpha