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接触多溴二苯醚(PBDE)会选择性地影响自闭症儿童的免疫反应。

exposure to polybrominated diphenyl ether (PBDE) selectively affects the immune response in autistic children.

作者信息

Akintunde Marjannie Eloi, Lin Yan-Ping, Krakowiak Paula, Pessah Isaac N, Hertz-Picciotto Irva, Puschner Birgit, Ashwood Paul, Van de Water Judy

机构信息

School of Medicine, Division of Rheumatology, Allergy and Clinical Immunology, University of California, Davis, United States.

NIEHS Center for Children's Environmental Health, University of California, Davis, United States.

出版信息

Brain Behav Immun Health. 2023 Oct 28;34:100697. doi: 10.1016/j.bbih.2023.100697. eCollection 2023 Dec.

Abstract

Children on the autism spectrum have been shown to have immune dysregulation that often correlates with behavioral deficits. The role of the post-natal environment in this dysregulation is an area of active investigation. We examined the association between plasma levels of polybrominated diphenyl ether (PBDE) and immune cell function in age-matched autistic children and non-autistic controls. Plasma from children on the autism spectrum (n = 38) and typically developing controls (TD; n = 60) were analyzed for 14 major PBDE congeners. Cytokine/chemokine production was measured in peripheral blood mononuclear cell (PBMC) supernatants with and without BDE-49 exposure. Total plasma concentration (∑) and individual congener levels were also correlated with T cell function. ∑ did not differ between diagnostic groups but correlated with reduced immune function in children on the autism spectrum. In autistic children, IL-2 and IFN-γ production was reduced in association with several individual BDE congeners, especially BDE-49 (p = 0.001). Furthermore, when PBMCs were exposed to BDE-49, cells from autistic children produced elevated levels of IL-6, TNF-α, IL-1β, MIP-1α and MCP-1 (p < 0.05). Therefore, despite similar plasma levels of PBDE, these data suggest that PBMC function was differentially impacted in the context of several PBDE congeners in autistic children relative to TD children where increased body burden of PBDE significantly correlated with a suppressed immune response in autistic children but not TD controls. Further, acute exposure of PBMCs to BDE-49 stimulates an elevated cytokine response in AU cases versus a depressed response in TD controls. These data suggest that exposure to the toxicant BDE-49 differentially impacts immune cell function in autistic children relative to TD children providing evidence for an underlying association between susceptibility to PBDE exposure and immune anomalies in children on the autism spectrum.

摘要

自闭症谱系障碍儿童已被证明存在免疫失调,这通常与行为缺陷相关。产后环境在这种失调中的作用是一个正在积极研究的领域。我们研究了年龄匹配的自闭症儿童和非自闭症对照中多溴二苯醚(PBDE)血浆水平与免疫细胞功能之间的关联。分析了自闭症谱系障碍儿童(n = 38)和发育正常对照(TD;n = 60)的血浆中14种主要PBDE同系物。在有和没有BDE - 49暴露的情况下,测量外周血单核细胞(PBMC)上清液中的细胞因子/趋化因子产生。总血浆浓度(∑)和单个同系物水平也与T细胞功能相关。诊断组之间的∑没有差异,但与自闭症谱系障碍儿童免疫功能降低相关。在自闭症儿童中,与几种单个BDE同系物,特别是BDE - 49相关联,IL - 2和IFN - γ的产生减少(p = 0.001)。此外,当PBMC暴露于BDE - 49时,自闭症儿童的细胞产生升高水平的IL - 6、TNF - α、IL - 1β、MIP - 1α和MCP - 1(p < 0.05)。因此,尽管PBDE的血浆水平相似,但这些数据表明,相对于TD儿童,自闭症儿童中几种PBDE同系物对PBMC功能的影响不同,其中PBDE身体负担增加与自闭症儿童免疫反应受抑制显著相关,而TD对照则不然。此外,PBMC急性暴露于BDE - 49会刺激自闭症病例中细胞因子反应升高,而TD对照中则反应降低。这些数据表明,与TD儿童相比,接触有毒物质BDE - 49对自闭症儿童免疫细胞功能的影响不同,为自闭症谱系障碍儿童对PBDE暴露的易感性与免疫异常之间的潜在关联提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f277/10654005/0ac4c2adb731/gr1.jpg

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