Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls.
Dysregulation of chemo-cytokine production in schizophrenic patients versus healthy controls.
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DOI：
10.1186/1471-2202-12-13
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发表时间：
2011-01-25
期刊：
影响因子：
2.4
通讯作者：
Grilli A
中科院分区：
文献类型：
--
作者：
Reale M;Patruno A;De Lutiis MA;Pesce M;Felaco M;Di Giannantonio M;Di Nicola M;Grilli A
精神分裂症的确切原因尚不清楚，尽管对这种疾病提出了几种病因学理论，包括发育或神经退化过程、神经递质异常、病毒感染和免疫功能障碍或自身免疫机制。越来越多的证据表明，特定的细胞因子和趋化因子在向大脑发出信号以产生神经化学、神经内分泌、神经免疫和行为变化方面发挥作用。炎症与精神分裂症之间的关系得到了精神分裂症患者血液和脑脊液中细胞因子的异常产生、细胞因子和细胞因子受体的异常浓度的支持。由于精神分裂症的神经病理最近被报道与小胶质细胞的激活密切相关，我们的目的是确定精神分裂症患者与健康对照组相比，是否存在自发或脂多糖诱导的外周血单核细胞趋化因子和细胞因子产生的失调。采用双抗体夹心法测定51例首发精神分裂症患者(SC)和40例健康人(HC)外周血单个核细胞培养上清液中单核细胞趋化蛋白-1(MCP1)、单核细胞趋化蛋白-1(MIP1)α、白介素8(IL-8)、白介素18(IL-18)、干扰素-γ和血管紧张素转换酶(RANTES)水平。在同步定量中，我们发现SC患者的单核细胞趋化蛋白-1、巨噬细胞炎性蛋白-1α、IL-8和IL-18水平显著高于HC患者，而其释放的RANTES和干扰素γ水平显著低于HC患者。在接受利培酮治疗的10例SC患者中，奥氮平或氯氮平基础和内毒素诱导的RANTES和IL-18的产生增加，而基础和内毒素诱导的MCP-1的产生均减少。治疗后血清水平差异无统计学意义。在精神分裂症患者中，PBMC产生选定的化学细胞因子是失调的，这一观察结果强化了外周细胞趋化因子网络参与精神分裂症病理生理学的假设。这些初步但有希望的数据支持更广泛的剖析方法的应用，以确定生物标记物作为精神疾病分析的诊断工具。
The exact cause of schizophrenia is not known, although several aetiological theories have been proposed for the disease, including developmental or neurodegenerative processes, neurotransmitter abnormalities, viral infection and immune dysfunction or autoimmune mechanisms. Growing evidence suggests that specific cytokines and chemokines play a role in signalling the brain to produce neurochemical, neuroendocrine, neuroimmune and behavioural changes. A relationship between inflammation and schizophrenia was supported by abnormal cytokines production, abnormal concentrations of cytokines and cytokine receptors in the blood and cerebrospinal fluid in schizophrenia. Since the neuropathology of schizophrenia has recently been reported to be closely associated with microglial activation we aimed to determined whether spontaneous or LPS-induced peripheral blood mononuclear cell chemokines and cytokines production is dysregulated in schizophrenic patients compared to healthy subjects. We enrolled 51 untreated first-episode schizophrenics (SC) and 40 healthy subjects (HC) and the levels of MCP-1, MIP-1α, IL-8, IL-18, IFN-γ and RANTES were determined by Elisa method in cell-free supernatants of PBMC cultures. In the simultaneous quantification we found significantly higher levels of constitutively and LPS-induced MCP-1, MIP-1α, IL-8 and IL-18, and lower RANTES and IFNγ levels released by PBMC of SC patients compared with HC. In ten SC patients receiving therapy with risperidone, olanzapine or clozapine basal and LPS-induced production of RANTES and IL-18 was increased, while both basal and LPS-induced MCP-1 production was decreased. No statistically significant differences were detected in serum levels after therapy. The observation that in schizophrenic patients the PBMC production of selected chemo-cytokines is dysregulated reinforces the hypothesis that the peripheral cyto-chemokine network is involved in the pathophysiology of schizophrenia. These preliminary, but promising data are supportive of the application of wider profiling approaches to the identification of biomarker as diagnostic tools for the analysis of psychiatric diseases.
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