Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Nian, Min; Zhou, Wei; Feng, Yuanming; Wang, Yan; Chen, Qian; Zhang, Jun

doi:10.1038/s41598-022-10501-8

Cited by 24 publications

(10 citation statements)

References 41 publications

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“…In conclusion, in line with the conclusion made by Nian et al [ 98 ], inconsistencies in the effects on Th1/Th2 cytokine levels exist between various studies. Unfortunately, there are no studies that identify the specific cell types involved or link the cytokine changes to the suppression of the antibody response.…”

Section: Resultssupporting

confidence: 82%

“…In a human study [ 98 ], 21 PFAS were identified in 198 Chinese women of childbearing age. In single PFAS models, PFAS were positively associated with Th1 and regulatory T-cell (Treg) cytokines, and negatively associated with Th2 and Th17 cytokines.…”

Section: Resultsmentioning

confidence: 99%

“…It should however be noted, that the effect of PFAS on cytokine homeostasis in humans is poorly understood [ 34 , 55 , 99 – 101 ]. Nian and co-workers point out, that evidence so far has been inconsistent, as also positive correlations between PFAS and Th2 cytokines in humans were shown [ 98 ].…”

Section: Resultsmentioning

confidence: 99%

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Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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Background Per- and polyfluoroalkyl substances (PFAS) are of public health concern, because of their ubiquitous and extremely persistent occurrence, and depending on their structure, their bio-accumulative, mobile and toxic properties. Human health effects associated with exposure to PFAS include adverse effects on the immune system. In 2020, EFSA (the European Food Safety Authority) defined adverse effects on the immune system as the most critical effect for human health risk assessment, based on reduced antibody responses to childhood vaccines and similar effects observed in experimental animal studies. Likewise, the U.S. EPA (Environmental Protection Agency) considers PFAS-induced immunotoxicity, especially in children, as the critical effect for risk assessment. However, the mechanisms by which antibody concentrations are impacted are not completely understood. Furthermore, other targets of the immune system functions have been reported in the literature. Objective The aim of this review is to explore PFAS-associated immune-related effects. This includes, relevant mechanisms that may underlie the observed effects on the immune system, immunosuppression as well as immunoenhancement, such as i) modulation of cell signalling and nuclear receptors, such as NF-κB and PPARs; ii) alteration of calcium signalling and homoeostasis in immune cells; iii) modulation of immune cell populations; iv) oxidative stress and v) impact on fatty acid metabolism & secondary effects on the immune system. Methods A literature research was conducted using three databases (Web of Science, PubMed, and Scopus), which were searched in July 2021 for relevant studies published in the time frame from 2018 to 2021. In total, 487 publications were identified as potentially eligible and following expert-based judgement, articles relevant for mechanisms of PFAS induced immunotoxicity are discussed. Conclusions Taken together, we show that there is substantial evidence from both in vitro and in vivo experimental as well as epidemiological studies, supporting that various PFAS, not only PFOA and PFOS, affect multiple aspects of the immune system. Timing of exposure is critical, because the developing immune system is especially vulnerable to toxic insults, resulting in a higher risk of particularly adverse immune effects but also other organs later in life.

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Section: Resultssupporting

confidence: 82%

Section: Resultsmentioning

confidence: 99%

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Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

et al. 2023

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“…In the study of 198 Chinese women of childbearing age, PFAS (specifically PFHxS, PFOS, and PFOA) were positively associated with TNF-α and IFN-γ, and negatively associated with IL-10 in both single and mixture analysis using BKMR. 24 Additionally, postnatal PFNA and prenatal PFOS were negatively linked with anti-inflammatory cytokines in children from 1,101 mothers-child pairs in the Human Early Life Exposome project (HELIX). 21 However, in a cohort of 103 pregnant women who were overweight or obese in the United States, 22 a consistent and positive relationship between serum PFOA, PFOS, and the sum of PFAS was observed with first and second trimester plasma concentrations of IL-6, with inconsistent and nonsignificant results for IL-10 and TNF-α.…”

Section: ■ Discussionmentioning

confidence: 99%

“…21,22,24−26 Specifically, PFAS levels were positively associated with Th1 cytokines (TNF-α and IFN-γ) and negatively associated with Th2 cytokines (IL-10). [22][23][24][25]27 However, most of these studies showed inconsistent results, and few have examined the joint effect of multiple PFAS. While these studies have failed to account for the fact that individuals are exposed to multiple PFAS simultaneously, they suggested that PFAS exposures disrupt the balance between inflammatory cytokines, with potential implications for maternal and child health.…”

Section: ■ Introductionmentioning

confidence: 99%

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal–Child Cohort

Tan,

Taibl,

Dunlop

et al. 2023

Environ. Sci. Technol.

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Per-and polyfluoroalkyl substances (PFAS) have been identified as environmental contributors to adverse birth outcomes. One potential mechanistic pathway could be through PFAS-related inflammation and cytokine production. Here, we examined associations between a PFAS mixture and inflammatory biomarkers during early and late pregnancy from participants enrolled in the Atlanta African American Maternal−Child Cohort (N = 425). Serum concentrations of multiple PFAS were detected in >90% samples at 8−14 weeks gestation. Serum concentrations of interferon-γ (IFN-γ), interleukin 6 (IL-6), interleukin 10 (IL-10), tumor necrosis factor-α (TNF-α), and C-reactive protein (CRP) were measured at up to two time points (8−14 weeks and 24−30 weeks gestation). The effect of the PFAS mixture on each inflammatory biomarker was examined using quantile gcomputation, Bayesian kernel machine regression (BKMR), Bayesian Weighted Sums (BWS), and weighted quantile sum (WQS) regression. Across all models, the PFAS mixture was associated with increased IFN-γ, IL-10, and TNF-α at both time points, with the strongest effects being observed at 24−30 weeks. Using quantile g-computation, increasing concentrations of a PFAS mixture were associated with a 29% (95% confidence interval = 18.0%, 40.7%) increase in TNF-α at 24−30 weeks. Similarly, using BWS, the PFAS mixture was associated with increased TNF-α at 24−30 weeks (summed effect = 0.29, 95% highest posterior density = 0.17, 0.41). The PFAS mixture was also positively associated with TNF-α at 24−30 weeks using BKMR [75th vs 50th percentile: 17.1% (95% credible interval = 7.7%, 27.4%)]. Meanwhile, PFOS was consistently the main drivers of overall mixture effect across four methods. Our findings indicated an increase in prenatal PFAS exposure is associated with an increase in multiple pro-inflammatory cytokines, potentially contributing to adverse pregnancy outcomes.

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Associations of legacy perfluoroalkyl and polyfluoroalkyl substances, alternatives, and isomers with gestational diabetes mellitus and glucose homeostasis among women conceiving through assisted reproduction in Shanghai, China

Mao,

Ding,

Wang

et al. 2024

Environ Sci Pollut Res

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Emerging and legacy PFAS and cytokine homeostasis in women of childbearing age

Cited by 24 publications

References 41 publications

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Consideration of pathways for immunotoxicity of per- and polyfluoroalkyl substances (PFAS)

Association between a Mixture of Per- and Polyfluoroalkyl Substances (PFAS) and Inflammatory Biomarkers in the Atlanta African American Maternal–Child Cohort

Associations of legacy perfluoroalkyl and polyfluoroalkyl substances, alternatives, and isomers with gestational diabetes mellitus and glucose homeostasis among women conceiving through assisted reproduction in Shanghai, China

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