Increased production of tumor necrosis factor-alpha TNF-alpha by IUGR human placentae

Objective: To evaluate the effect of pathological placental conditions such as intrauterine growth restriction (IUGR) or exposure to angiotensin II (A II) on TNF-alpha secretion in the vasculature of isolated human placental c otyledons. Study design: Isolated placental cotyledons from 10 normal and f our intrauterine growth restricted fetuses were dually perfused. Perfusate samples from the fetal circulation were collected every 30 min during 120 m in. TNF-alpha levels in the fetal-placental perfusate were evaluated using specific commercial ELISA kits. In three additional normal placentae, bolus injections of angiotensin II (10(-9)-10(-4) mol/l) were given into the Fet al-placental circulation and perfusate samples were collected. Statistical significance of difference TNF-alpha levels between different conditions wa s determined by analysis of variance (ANOVA) and paired t-test. Results: TN F-alpha levels were significantly higher in the perfusate of IUGR placentae as compared with normal placentae after 120 min of perfusion (mean 410+/-1 21 vs. 39+/-14 pg/ml, P = 0.005). There was a significant dose-dependent in crease in TNF-alpha levels in the placental perfusate after a bolus injecti on of AII 66 pg/ml with AII 10(-9) mol/l vs. 97 pg/ml with AII 10(-5) mol/l (P = 0.004). respectively. Conclusions: Placental pathology related to con dition IUGR might induce the secretion of proinflammatory cytokines such as TNF-alpha, which may enhance the vasoconstriction of the Fetal placental v ascular bed. (C) 2001 Elsevier Science Ireland Ltd. All rights reserved.