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产前血液金属、全氟和多氟烷基物质与抗原或有丝分裂原刺激脐带血淋巴细胞增殖和细胞因子分泌。

Prenatal blood metals, per- and polyfluoroalkyl substances and antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion.

机构信息

Department of Epidemiology and Population Health, Stanford Medicine, Stanford, CA, USA.

Division of Chronic Disease Research Across the Lifecourse, Department of Population Medicine, Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA, USA.

出版信息

Environ Res. 2024 Oct 15;259:119555. doi: 10.1016/j.envres.2024.119555. Epub 2024 Jul 3.

Abstract

BACKGROUND

Evidence suggests that prenatal per- and polyfluoroalkyl substances (PFAS) and metals, two classes of chemicals found ubiquitously in human populations, influence immune system development and response.

OBJECTIVE

We evaluated whether first trimester blood PFAS and metals were associated with antigen- or mitogen-stimulated cord blood lymphocyte proliferation and cytokine secretion.

METHODS

We measured six PFAS, as well as six nonessential and four essential metals, in first trimester blood from participants in the longitudinal pre-birth Project Viva cohort, recruited between 1999 and 2000 in eastern Massachusetts. We measured antigen- or mitogen-stimulated cord blood mononuclear cell proliferation responses (n = 269-314) and cytokine secretion (n = 217-302). We used covariate-adjusted least absolute shrinkage and selection operator (LASSO) for variable selection and multivariable regression to estimate associations with the immune markers.

RESULTS

Each ng/mL of MeFOSAA was associated with a 3.6% (1.4, 5.8) higher lymphocyte proliferation response after stimulation with egg antigen, as well as 0.8 (0.7, 1.0) reduced odds of having IFN-γ detected in response to dust mite. Each ng/g increment of cesium was associated with 27.8% (-45.1, -4.9) lower IL-10 levels in response to dust mite. Each ng/g increment of mercury was associated with 12.0% (1.3, 23.8) higher IL-13 levels in response to mitogen PHA. Each ng/g increment of selenium and zinc was associated with 0.2% (0.01, 0.4) and 0.01% (0.002, 0.02) higher TNF-α in response to mitogen PHA, respectively.

CONCLUSIONS

Prenatal metals and PFAS influence cord blood lymphocyte proliferation and cytokine secretion in ways that may increase risk for atopic disease in childhood.

摘要

背景

有证据表明,围产期全氟和多氟烷基物质(PFAS)和金属这两类在人群中普遍存在的化学物质会影响免疫系统的发育和反应。

目的

我们评估了妊娠早期血液中的 PFAS 和金属是否与抗原或有丝分裂原刺激脐血淋巴细胞增殖和细胞因子分泌有关。

方法

我们测量了来自纵向孕前项目 Viva 队列参与者的妊娠早期血液中的 6 种 PFAS,以及 6 种非必需和 4 种必需金属。我们测量了抗原或有丝分裂原刺激的脐血单个核细胞增殖反应(n=269-314)和细胞因子分泌(n=217-302)。我们使用了协变量调整的最小绝对收缩和选择算子(LASSO)进行变量选择和多变量回归,以估计与免疫标志物的关联。

结果

每 ng/mL 的 MeFOSAA 与卵抗原刺激后的淋巴细胞增殖反应增加 3.6%(1.4,5.8)有关,与尘螨刺激后 IFN-γ检测减少 0.8%(0.7,1.0)有关。每 ng/g 递增的铯与尘螨刺激后 IL-10 水平降低 27.8%(-45.1,-4.9)有关。每 ng/g 递增的汞与有丝分裂原 PHA 刺激后 IL-13 水平升高 12.0%(1.3,23.8)有关。每 ng/g 递增的硒和锌与有丝分裂原 PHA 刺激后 TNF-α 水平分别升高 0.2%(0.01,0.4)和 0.01%(0.002,0.02)有关。

结论

围产期金属和 PFAS 以可能增加儿童特应性疾病风险的方式影响脐血淋巴细胞增殖和细胞因子分泌。

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