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精神分裂症患者未刺激和有丝分裂原刺激外周血单个核细胞中的体外细胞因子合成。

In vitro cytokine synthesis in unstimulated and mitogen-stimulated peripheral blood mononuclear cells from individuals with schizophrenia.

机构信息

Department of Experimental Immunology, Medical University of Lodz, Lodz, Poland.

Department of Old Age Psychiatry and Psychotic Disorders, Medical University of Lodz, Lodz, Poland.

出版信息

J Investig Med. 2019 Oct;67(7):1053-1060. doi: 10.1136/jim-2018-000964. Epub 2019 May 2.

Abstract

Increasing evidence has shown that the immune system is involved in the schizophrenia development, with alterations in immune cell reactivity being one possible factor contributing to its pathogenesis. The purpose of the study was to evaluate in vitro the capability of peripheral blood mononuclear cells (PBMCs) obtained from subjects with schizophrenia and controls to engage in spontaneous and phytohemagglutinin (PHA)-stimulated cytokine production. The concentrations of various cytokines (interleukin (IL)-1β, IL-17A, tumor necrosis factor (TNF), interferon (IFN)-γ and IL-10) in supernatants from cultured PBMCs were measured using the cytometric bead array. No significant differences in the spontaneous production of IL-1β, IL-17A, IFN-γ and IL-10 by PBMCs were detected between individuals with schizophrenia and controls. TNF synthesis by PBMCs was found to be lower among those with schizophrenia. In all subjects and controls, greater cytokine generation was associated with PBMCs treated with PHA compared with those that were not. The PBMCs from people with schizophrenia displayed considerably higher sensitivity to mitogen stimulation, as the production of IL-17A, TNF and IFN-γ was at least threefold of that observed in healthy subjects, which may be driven by antipsychotics taken by patients with schizophrenia. Correlation was observed between spontaneous production of IFN-γ and Positive and Negative Syndrome Scale G subscore (which measures the general symptoms of schizophrenia) and between PHA-stimulated synthesis of IL-17A and G subscore. Our data confirm that the immune system dysregulation may underlie schizophrenia pathophysiology. There is a potential possibility that immunological tests could be used as a diagnostic, therapeutic and side-effects biomarker for schizophrenia, but further studies are needed.

摘要

越来越多的证据表明免疫系统参与了精神分裂症的发展,免疫细胞反应的改变是导致其发病机制的一个可能因素。本研究旨在评估来自精神分裂症患者和对照组的外周血单个核细胞(PBMC)在体外自发和植物血凝素(PHA)刺激细胞因子产生的能力。使用细胞因子检测试剂盒测量培养的 PBMC 上清液中各种细胞因子(白细胞介素(IL)-1β、IL-17A、肿瘤坏死因子(TNF)、干扰素(IFN)-γ和 IL-10)的浓度。未发现精神分裂症患者和对照组之间 PBMC 自发产生 IL-1β、IL-17A、IFN-γ和 IL-10 有显著差异。发现精神分裂症患者的 PBMC 中 TNF 合成较低。在所有受试者和对照组中,与未经 PHA 处理的 PBMC 相比,用 PHA 处理的 PBMC 产生的细胞因子更多。精神分裂症患者的 PBMC 对有丝分裂原刺激的敏感性明显更高,因为 IL-17A、TNF 和 IFN-γ的产生至少是健康受试者的三倍,这可能是由于精神分裂症患者服用的抗精神病药物所致。在精神分裂症患者中,自发产生 IFN-γ与阳性和阴性综合征量表 G 分量表(用于衡量精神分裂症的一般症状)之间以及 PHA 刺激的 IL-17A 合成与 G 分量表之间存在相关性。我们的数据证实免疫系统失调可能是精神分裂症病理生理学的基础。有可能免疫测试可以作为精神分裂症的诊断、治疗和副作用生物标志物,但需要进一步的研究。

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