Using blood cytokine measures to define high inflammatory biotype of schizophrenia and schizoaffective disorder.
Using blood cytokine measures to define high inflammatory biotype of schizophrenia and schizoaffective disorder.
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DOI：
10.1186/s12974-017-0962-y
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发表时间：
2017-09-18
影响因子：
9.3
通讯作者：
Weickert CS
中科院分区：
文献类型：
--
作者：
Boerrigter D;Weickert TW;Lenroot R;O'Donnell M;Galletly C;Liu D;Burgess M;Cadiz R;Jacomb I;Catts VS;Fillman SG;Weickert CS
在精神分裂症患者的大脑和血液中发现了促炎细胞因子的增加。然而，增加的细胞因子在所有精神分裂症患者中并不明显，但在一个子集中发现。最好地定义该亚群的细胞因子变化，称为“升高的炎症生物型”，仍在鉴定中。采用定量RT-PCR方法，我们从健康对照组和精神分裂症或情感性精神障碍患者（n = 165）的外周血中检测了5种细胞因子mRNA（IL-1β、IL-2、IL-6、IL-8和IL-18）。我们使用转录水平的聚类分析来定义那些具有低水平和那些具有升高水平的细胞因子表达。使用基于Luminex Magpix的测定法测量了同一队列中血清和血浆中的8种细胞因子蛋白（IL-1β、IL-2、IL-6、IL-8、IL-10、IL-12、IFNγ和TNFα）。根据我们基于转录的聚类分析，我们比较了诊断组之间以及细胞因子表达水平低和升高的组之间的外周mRNA和蛋白质水平。我们发现，与健康对照组相比，精神分裂症患者的抗炎性IL-2 mRNA总体下降（p = 0.006），三种血清细胞因子IL-6（p = 0.010）、IL-8（p = 0.024）和TNFα（p < 0.001）升高。与健康对照组（33%）相比，精神分裂症患者（48%）被归类为炎症生物型升高。炎症生物型升高的人中IL-1β、IL-6、IL-8和IL-10 mRNA的增加幅度为非炎症生物型升高的人的100%至220%，并且在对照组和精神分裂症组之间相当。血液细胞因子蛋白水平与细胞因子mRNA水平无关，血浆中只有两种细胞因子水平可区分升高和低炎症生物型，IL-1β在升高的细胞因子对照组中显著升高，IL-8在升高的细胞因子精神分裂症组中显著升高。我们的研究结果证实，与对照组相比，精神分裂症患者更容易出现炎症水平升高。我们认为，基于外周测量来定义炎症状态的努力需要考虑mRNA和蛋白质测量，因为每种测量都有不同的优点和缺点，并且可以产生不同的结果。本文的在线版本（10.1186/s12974-017-0962-y）包含补充材料，可供授权用户使用。
Increases in pro-inflammatory cytokines are found in the brain and blood of people with schizophrenia. However, increased cytokines are not evident in all people with schizophrenia, but are found in a subset. The cytokine changes that best define this subset, termed the “elevated inflammatory biotype”, are still being identified. Using quantitative RT-PCR, we measured five cytokine mRNAs (IL-1β, IL-2 IL-6, IL-8 and IL-18) from peripheral blood of healthy controls and of people with schizophrenia or schizoaffective disorder (n = 165). We used a cluster analysis of the transcript levels to define those with low and those with elevated levels of cytokine expression. From the same cohort, eight cytokine proteins (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-12, IFNγ and TNFα) were measured in serum and plasma using a Luminex Magpix-based assay. We compared peripheral mRNA and protein levels across diagnostic groups and between those with low and elevated levels of cytokine expression according to our transcription-based cluster analysis. We found an overall decrease in the anti-inflammatory IL-2 mRNA (p = 0.006) and an increase in three serum cytokines, IL-6 (p = 0.010), IL-8 (p = 0.024) and TNFα (p < 0.001) in people with schizophrenia compared to healthy controls. A greater percentage of people with schizophrenia (48%) were categorised into the elevated inflammatory biotype compared to healthy controls (33%). The magnitude of increase in IL-1β, IL-6, IL-8 and IL-10 mRNAs in people in the elevated inflammation biotype ranged from 100 to 220% of those in the non-elevated inflammatory biotype and was comparable between control and schizophrenia groups. Blood cytokine protein levels did not correlate with cytokine mRNA levels, and plasma levels of only two cytokines distinguished the elevated and low inflammatory biotypes, with IL-1β significantly increased in the elevated cytokine control group and IL-8 significantly increased in the elevated cytokine schizophrenia group. Our results confirm that individuals with schizophrenia are more likely to have elevated levels of inflammation compared to controls. We suggest that efforts to define inflammatory status based on peripheral measures need to consider both mRNA and protein measures as each have distinct advantages and disadvantages and can yield different results. The online version of this article (10.1186/s12974-017-0962-y) contains supplementary material, which is available to authorized users.
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