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孕中期早期无感染证据的孕妇羊水和母血清细胞因子水平的差异

Differences in amniotic fluid and maternal serum cytokine levels in early midtrimester women without evidence of infection.

作者信息

Chow Sharon S W, Craig Maria E, Jones Cheryl A, Hall Beverley, Catteau Jacki, Lloyd Andrew R, Rawlinson William D

机构信息

School of Medical Sciences, University of New South Wales, 2052 NSW, Australia.

出版信息

Cytokine. 2008 Oct;44(1):78-84. doi: 10.1016/j.cyto.2008.06.009. Epub 2008 Aug 13.

DOI:10.1016/j.cyto.2008.06.009
PMID:18703348
Abstract

The amniotic fluid cytokine profile has been shown to be indicative of various disease states, and changes may be associated with preterm labor or infection. Anti-inflammatory cytokine profiles may be essential for successful normal pregnancy. However, there are currently few normative data on the concentration of cytokines in amniotic fluids during pregnancy. The aim of this study was to provide new amniotic fluid cytokine data for future comparative studies in disease states, notably in utero viral infections, and to compare these with maternal serum levels. Amniotic fluid was obtained from 100 pregnant women undergoing elective amniocentesis at the Royal Hospital for Women, Randwick. Concentrations of 27 cytokines were simultaneously measured in amniotic fluid and a subset of matching maternal sera (n=33) using a multiplex bead-based immunoassay system (Bio-Plex, Bio-Rad). To exclude infection, nested multiplex PCR targeting 17 known congenital infectious agents were performed on all amniotic fluid and maternal serum samples, and serological testing was also performed against some of these agents. Maternal serum concentration was positively correlated with amniotic fluid levels for MIP-1beta (r=0.39, P=0.027). IL-1ra was positively correlated to maternal age (r=0.210, P=0.036), and mean IL-5 levels were significantly higher in amniotic fluids from pregnancies with male fetuses than those with female fetuses (P=0.036). Normal amniotic fluid concentrations for five cytokines (IL-6, IL-8, IP-10, MCP-1, IL-1ra) were found to be significantly elevated over maternal serum concentrations in matched pairs (P<0.05). Concentrations of 12 cytokines (eotaxin, IFN-gamma, IL-9, IL-12, IL-15, IL-17, MIP-1alpha, MIP-1beta, RANTES, TNF-alpha, VEGF, PDGF bb) were significantly elevated in maternal serum compared to paired amniotic fluid at midtrimester (P<0.05). Amniotic fluid may be more representative of the fetal cytokine profile than cytokine analysis on antenatal sera as it represents predominantly fetal urinary and respiratory secretions. This study provides new normative data for multiple cytokine levels in amniotic fluid and maternal sera at 14-16 weeks gestation, and is a valuable tool for future diagnostic and comparative studies.

摘要

羊水细胞因子谱已被证明可指示各种疾病状态,其变化可能与早产或感染有关。抗炎细胞因子谱对于正常妊娠的成功可能至关重要。然而,目前关于孕期羊水细胞因子浓度的规范数据很少。本研究的目的是为未来疾病状态的比较研究,特别是宫内病毒感染的研究,提供新的羊水细胞因子数据,并将其与母体血清水平进行比较。从兰德威克皇家妇女医院接受选择性羊膜穿刺术的100名孕妇中获取羊水。使用基于微珠的多重免疫分析系统(Bio-Plex,伯乐公司)同时测量羊水中27种细胞因子的浓度以及一部分匹配的母体血清(n = 33)中的浓度。为排除感染,对所有羊水和母体血清样本进行针对17种已知先天性感染因子的巢式多重聚合酶链反应,并针对其中一些因子进行血清学检测。母体血清浓度与羊水MIP-1β水平呈正相关(r = 0.39,P = 0.027)。IL-1ra与产妇年龄呈正相关(r = 0.210,P = 0.036),男性胎儿妊娠的羊水平均IL-5水平显著高于女性胎儿妊娠的羊水(P = 0.036)。发现五种细胞因子(IL-6、IL-8、IP-10、MCP-1、IL-1ra)的正常羊水浓度在配对样本中显著高于母体血清浓度(P < 0.05)。与孕中期配对羊水相比,母体血清中12种细胞因子(嗜酸性粒细胞趋化因子、IFN-γ、IL-9、IL-12、IL-15、IL-17、MIP-1α、MIP-1β、RANTES、TNF-α、VEGF、PDGF bb)的浓度显著升高(P < 0.05)。羊水可能比产前血清的细胞因子分析更能代表胎儿的细胞因子谱,因为它主要代表胎儿的尿液和呼吸道分泌物。本研究提供了妊娠14 - 16周时羊水和母体血清中多种细胞因子水平的新规范数据,是未来诊断和比较研究的宝贵工具。

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