Maternal plasma cytokines in early- and mid-gestation of normal human pregnancy and their association with maternal factors

Maternal plasma cytokines in early- and mid-gestation of normal human pregnancy and their association with maternal factors
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DOI:
10.1016/j.jri.2007.06.051
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发表时间:
2008-04-01
影响因子:
3.4
通讯作者:
Thorsen, P.
Thorsen, P.
中科院分区:
医学4区
文献类型:
--
作者:
Curry, A. E.;Vogel, I.;Thorsen, P.

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很少有研究评估正常妊娠期间循环细胞因子水平的纵向变化。我们在一个大型纵向队列中研究了从怀孕早期到中期母体血浆细胞因子的自然史。使用多重流式细胞术测量早期(中位[IQR]:8.5周[7.1,10.0])和中期(25.0 [24.1, 26.1])来自 1274 名分娩单胎足月婴儿的丹麦妇女。 GM-CSF 从怀孕早期到中期下降(中位百分比变化 [95% CI]:-51.3% [-59.1%, -41.8%]),而 IL-6(24.3% [4.6%, 43.9%])、IL-12(21.3% [8.9%, 35.7%])和 IFN-gamma(131.7%)则增加[100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) 和 TNF-α-(0% [-5.9%, 25.6%]) 保持稳定。在妊娠早期和中期,所有细胞因子之间均发现正相关(所有 p < 0.001)。妊娠早期和中期的 IL-2、IL-12、TNF-α 和 GM-CSF 水平呈等级相关,但 IL-6 和 IFN-γ 则不呈等级相关;这些相关性通常弱于妊娠单个时间点不同细胞因子之间的相关性。与其他 BMI 类别的女性相比,孕前 BMI < 18.5 的女性 IFN-γ 和 GM-CSF 水平降低,而年龄 >= 35 岁的女性 IL-2、IL-6、TNF-α 和 IFN-γ 水平升高。曾有过早产史的女性妊娠早期 TNF-α 水平较高。细胞因子水平与妊娠无关。总之,在妊娠早期和中期血浆中检测到了细胞因子,IL-6、IL-12、IFN-γ和GM-CSF浓度在整个妊娠期间有所不同。浓度可能取决于体重指数、母亲年龄和既往早产情况。 (C) 2007 Elsevier Ireland Ltd. 保留所有权利。
Few studies have assessed longitudinal changes in circulating cytokine levels during normal pregnancy. We have examined the natural history of maternal plasma cytokines from early-to mid-pregnancy in a large, longitudinal cohort. Multiplex flow cytometry was used to measure interleukin (IL)-2, IL-6, IL-12, tumor necrosis factor (TNF)-alpha, interferon (IFN)-gamma and granulocyte-macrophage colony-stimulating factor (GM-CSF) in early-(median [IQR]: 8.5 weeks [7.1, 10.0]) and mid-pregnancy (25.0 [24.1, 26.1]) from 1274 Danish women delivering singleton term infants. GM-CSF decreased from early-to mid-pregnancy (median percent change [95% CI]: -51.3% [-59.1%, -41.8%]), while increases were observed in IL-6 (24.3% [4.6%, 43.9%]), IL-12 (21.3% [8.9%, 35.7%]) and IFN-gamma (131.7% [100.2%, 171.6%]); IL-2 (-2.8% [-11.5%, 0.0%]) and TNF-alpha-(0% [-5.9%, 25.6%]) remained stable. Positive correlations were found between all cytokines, both in early-and mid-pregnancy (all p < 0.001). Early-and mid-pregnancy levels were rank-correlated for IL-2, IL-12, TNF-alpha and GM-CSF, but not IL-6 and IFN-gamma; these correlations were generally weaker than correlations between different cytokines at a single time point in pregnancy. Women with a pre-pregnancy BMI < 18.5 had reduced levels of IFN-gamma and GM-CSF compared to women in other BMI categories, while women aged >= 35 years had elevated IL-2, IL-6, TNF-alpha and IFN-gamma. Early-pregnancy levels of TNF-alpha-were higher in women with a prior preterm delivery. Cytokine levels were not associated with gravidity. In conclusion, cytokines were detected in plasma during early-and mid-pregnancy, with IL-6, IL-12, IFN-gamma and GM-CSF concentrations varying over pregnancy. Concentrations may depend on BMI, maternal age and prior preterm delivery. (C) 2007 Elsevier Ireland Ltd. All rights reserved.