The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia
The Interaction of Nuclear Factor-Kappa B and Cytokines Is Associated with Schizophrenia
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核因子-κ B 和细胞因子的相互作用与精神分裂症有关
DOI：
10.1016/j.biopsych.2008.10.018
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发表时间：
2009-03-15
影响因子：
10.6
通讯作者：
Zhao, Jing-Ping
中科院分区：
文献类型：
--
作者：
Song, Xue-Qin;Lv, Lu-Xian;Zhao, Jing-Ping
背景资料：许多研究表明精神分裂症与细胞因子介导的炎症反应有关，核因子-κ B（NF-κ B）调节细胞因子的表达。然而，目前还不清楚是否NF-κ B和细胞因子之间的相互作用是牵连在精神分裂症和精神抑制剂治疗4周的效果是否与cytokines.Methods的改变：65例健康受试者和83例首发精神分裂症患者谁符合DSM-IV标准，谁从来没有用精神抑制剂治疗以前被包括在内。采用夹心酶免疫法（EIA）检测血清细胞因子如白细胞介素-1 β（IL-1 β）和肿瘤坏死因子-α（TNF-α）水平。采用半定量逆转录聚合酶链反应（RT-PCR）检测外周血单个核细胞（PBMC）细胞因子（IL-1 β、TNF-α）和NF-κ B（B）mRNA的表达。结果：精神分裂症患者血清IL-1 β和TNF-α水平及PBMC mRNA表达水平均显著高于健康对照组。然而，用抗精神病药利培酮治疗4周可显著降低精神分裂症患者血清IL-1 β水平和PBMC mRNA表达。患者外周血NF-κ B B活性和PBMC mRNA表达水平均显著高于健康对照组。此外，精神分裂症患者和健康对照组PBMC中IL-1 β和TNF-α mRNA表达与NF-κ B B活化呈正相关。结论：精神分裂症患者存在细胞因子系统激活和免疫功能紊乱。NF-κ B活化可能通过与细胞因子相互作用在精神分裂症中发挥关键作用。
Background: Many reports suggest that schizophrenia is associated with the inflammatory response mediated by cytokines, and nuclear factor-kappa B (NF-kappa B) regulates the expression of cytokines. However, it remains unclear whether the interaction between NF-kappa B and cytokines is implicated in schizophrenia and whether the effect of neuroleptics treatment for 4 weeks is associated with the alteration of cytokines.Methods: Sixty-five healthy subjects and 83 first-episode schizophrenic patients who met DSM-IV criteria and who were never treated with neuroleptics previously were included. Serum levels of cytokines such as interleukin-1 beta (IL-1 beta) and tumor necrosis factor-alpha (TNF-alpha) were examined by using sandwich enzyme immunoassay (EIA). Peripheral blood mononuclear cell (PBMC) mRNA expressions of cytokines (IL-1 beta, TNF-alpha) and NF-kappa B were detected by using semiquantitative reverse transcription polymerase chain reaction (RT-PCR). NF-kappa B activation was examined by using transcription factor assay kits.Results: Schizophrenic patients showed significantly higher serum levels and PBMC mRNA expressions of IL-1 beta and TNF-alpha compared with healthy subjects. However, treatment with the neuroleptic risperidone for 4 weeks significantly decreased serum levels and PBMC mRNA expressions of IL-1 beta in schizophrenic patients. NF-kappa B activation and PBMC mRNA expression in patients were significantly higher than those in healthy subjects. Furthermore, PBMC mRNA expressions of IL-1 beta and TNF-alpha were positively correlated to NF-kappa B activation in both schizophrenic patients and healthy control subjects.Conclusions: Schizophrenic patients showed activation of the cytokine system and immune disturbance. NF-kappa B activation may play a pivotal role in schizophrenia through interaction with cytokines.