Placental Secretion of Interleukin-1 and Interleukin-1 Receptor Antagonist in Preeclampsia: Effect of Magnesium Sulfate
Placental Secretion of Interleukin-1 and Interleukin-1 Receptor Antagonist in Preeclampsia: Effect of Magnesium Sulfate
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DOI：
10.1089/jir.2012.0013
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发表时间：
2012-09-01
影响因子：
2.3
通讯作者：
Huleihel, Mahmoud
中科院分区：
文献类型：
--
作者：
Amash, Alaa;Holcberg, Gershon;Huleihel, Mahmoud
先兆子痫是一种妊娠特异性疾病，其特征是高血压和全身内皮功能障碍。白细胞介素 (IL)-1 β 可能是子痫前期母体内皮功能障碍的介质。据报道，先兆子痫女性的血清 IL-1 β 及其天然抑制剂 IL-1 受体拮抗剂 (IL-1Ra) 升高。在当前的研究中，我们探讨了胎盘在先兆子痫中控制 IL-1β 及其天然抑制剂 IL-1Ra 循环水平的作用，以及硫酸镁 (MgSO4) 对这些水平的可能影响。使用离体胎盘灌注系统，在存在或不存在 MgSO4 的情况下对先兆子痫 (n = 9) 和血压正常 (n = 6) 妊娠的胎盘进行灌注。从灌注系统的母体和胎儿循环中收集灌注液样品，并通过酶联免疫分析（ELISA）检测IL-1β和IL-1Ra。与血压正常的胎盘相比，先兆子痫胎盘分泌的IL-1β水平较高（P<0.001），并且IL-1Ra水平倾向于较高，主要进入母体循环，但未检测到IL-1β：IL-1Ra比率存在差异。然而，与血压正常的胎盘相比，先兆子痫胎盘胎儿循环中IL-1β或IL-1Ra的分泌水平仅有倾向性增加。对先兆子痫胎盘施用 MgSO4 导致母体循环中 IL-1β 分泌增加的减弱（P < 0.001），并且导致 IL-1Ra 的倾向性减少。然而，先兆子痫胎盘中IL-1β：IL-1Ra的比率不受MgSO4的影响。有趣的是，血压正常的胎盘暴露于 MgSO4 仅导致母体循环中 IL-1Ra 水平升高，而不影响 IL-1β 水平或 IL-1β: IL-1Ra 比率。这些发现表明，胎盘可能通过增加向母体循环中分泌这些细胞因子来导致先兆子痫中血清IL-1β和IL-1Ra的升高，并且MgSO4能够减弱先兆子痫中IL-1β和可能的IL-1Ra的这种增加的分泌。
Preeclampsia is a pregnancy-specific disorder characterized by hypertension and systemic endothelial dysfunction. Interleukin (IL)-1 beta is a possible mediator of maternal endothelial dysfunction in preeclampsia. Serum IL-1 beta as well as its natural inhibitor IL-1 receptor antagonist (IL-1Ra) were reported to be increased in women with preeclampsia. In the current study, we addressed the role of the placenta in controlling the circulatory levels of IL-1 beta and its natural inhibitor IL-1Ra in preeclampsia, and the possible effect of magnesium sulfate (MgSO4) on these levels. Using an ex vivo placental perfusion system, placentas from preeclamptic (n = 9) and normotensive (n = 6) pregnancies were perfused in presence or absence of MgSO4. Perfusate samples were collected from the maternal and the fetal circulations of the perfusion system, and IL-1 beta and IL-1Ra were examined by enzyme-linked immunoassay (ELISA). Preeclamptic placentas secreted higher levels of IL-1 beta (P < 0.001), and a tendentious higher levels of IL-1Ra, mainly into the maternal circulation, as compared with normotensive placentas, although no differences in IL-1 beta: IL-1Ra ratio were detected. However, there was only tendentious increase in the secretion levels of IL-1 beta or IL-1Ra into the fetal circulation of preeclamptic placentas, when compared with normotensive placentas. Administration of MgSO4 to preeclamptic placentas resulted in an attenuation of the increased secretion of IL-1 beta into the maternal circulation (P < 0.001), and in a tendentious reduction in IL-1Ra. However, IL-1 beta: IL-1Ra ratio in preeclamptic placentas was not affected by MgSO4. Interestingly, exposure of normotensive placenta to MgSO4 resulted only in increased levels of IL-1Ra in the maternal circulation, without affecting IL-1 beta levels or IL-1 beta: IL-1Ra ratio. These findings suggest that the placenta may contribute to the elevation in serum IL-1 beta and IL-1Ra in preeclampsia by increased secretion of these cytokines into the maternal circulation, and that MgSO4 is able to attenuate this increased secretion of IL-1 beta, and possibly IL-1Ra, in preeclampsia.