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与妊娠肝内胆汁淤积症相关的血清炎症细胞因子谱。

Serum profiles of inflammatory cytokines associated with intrahepatic cholestasis of pregnancy.

机构信息

Department of Obstetrics, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

Department of Nursing, Shanghai First Maternity and Infant Hospital, School of Medicine, Tongji University, Shanghai 200092, China.

出版信息

J Matern Fetal Neonatal Med. 2022 Dec;35(25):10072-10081. doi: 10.1080/14767058.2022.2089551. Epub 2022 Jun 27.

DOI:10.1080/14767058.2022.2089551
PMID:35762044
Abstract

BACKGROUND

The pathogenesis of intrahepatic cholestasis of pregnancy (ICP) is not clear, and some researchers have compared the differences in serum levels of inflammatory cytokines between ICP patients and normal pregnant women, but there are few studies and different conclusions.

AIM

To investigate the levels of inflammatory cytokines such as interleukins (IL) -4, IL-6, IL-8, and tumor necrosis factor alpha (TNF-α) in patients with ICP and their potential role in pathophysiology.

METHODS

This case-control study was conducted in Shanghai First Maternity and Infant Health Hospital, and we recruited ICP patients and age-matched healthy pregnant women as a control group. Plasma samples from 40 subjects with ICP and 40 subjects without ICP were tested for concentration of the following inflammatory cytokines: interferon-gamma, IL-1 alpha, IL-1 beta, IL-2, IL-4, IL-6, IL-8, IL-10, and TNF-α. Analyzed inflammatory cytokines were then assessed, either individually or in combination with regard to ICP.

RESULTS

The cytokine composition of the ICP and CTL group was significantly different. We compared levels of inflammatory cytokines with regard to the presence of ICP symptoms. Levels of IL-4, IL-6, and TNF-α were significantly lower in ICP subjects, and IL-8 were significantly higher in ICP subjects, compared with CTL subjects. The TNF-α showed the best performance for ICP identification (area under the curve [AUC]: 0.829). Performance was increased when TNF-α was combined with IL-4 and IL-8 analysis (AUC, 0.901). Spearman correlation and linear regression analysis revealed that the TNF-α concentrations correlated with IL-4 and IL-6 levels, and inversely correlated to TBA, ALT, AST, and IL-8 levels.

CONCLUSION

IL-4, IL-6, and TNF-α were significantly decreased, while IL-8 was significantly increased in the ICP group compared with the healthy control group. TNF showed the best single marker discriminatory potential; however, combining TNF-α, IL-4, and IL-8 analyses increased performance for ICP identification.

摘要

背景

妊娠肝内胆汁淤积症(ICP)的发病机制尚不清楚,一些研究人员比较了 ICP 患者与正常孕妇血清中炎症细胞因子的差异,但研究较少,结论也不尽相同。

目的

探讨白细胞介素(IL)-4、IL-6、IL-8 和肿瘤坏死因子-α(TNF-α)等炎症细胞因子在 ICP 患者中的水平及其在病理生理学中的潜在作用。

方法

本病例对照研究在上海第一妇婴保健院进行,招募 ICP 患者和年龄匹配的健康孕妇作为对照组。检测 40 例 ICP 患者和 40 例非 ICP 患者的血浆样本中以下炎症细胞因子的浓度:干扰素-γ、IL-1α、IL-1β、IL-2、IL-4、IL-6、IL-8、IL-10 和 TNF-α。然后评估单个或组合的分析细胞因子与 ICP 的关系。

结果

ICP 和 CTL 组的细胞因子组成明显不同。我们比较了存在 ICP 症状时的炎症细胞因子水平。与 CTL 组相比,ICP 组的 IL-4、IL-6 和 TNF-α水平明显降低,IL-8 水平明显升高。TNF-α对 ICP 的识别具有最佳性能(曲线下面积[AUC]:0.829)。当 TNF-α与 IL-4 和 IL-8 分析相结合时,性能得到提高(AUC,0.901)。Spearman 相关和线性回归分析表明,TNF-α浓度与 IL-4 和 IL-6 水平相关,与 TBA、ALT、AST 和 IL-8 水平呈负相关。

结论

与健康对照组相比,ICP 组的 IL-4、IL-6 和 TNF-α水平显著降低,而 IL-8 水平显著升高。TNF-α 作为单一标志物具有最佳的鉴别潜力;然而,结合 TNF-α、IL-4 和 IL-8 分析可提高 ICP 识别的性能。

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