Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia

Increased M1/decreased M2 signature and signs of Th1/Th2 shift in chronic patients with bipolar disorder, but not in those with schizophrenia
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DOI:
10.1038/tp.2014.46
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发表时间:
2014-07-01
影响因子:
6.8
通讯作者:
Furlan, R.
Furlan, R.
中科院分区:
医学1区
文献类型:
--
作者:
Brambilla, P.;Bellani, M.;Furlan, R.

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我们在这里提出的数据,与健康对照组(HC,N = 20)相比,慢性患者患有精神分裂症(SCZ,N = 20)或双相情感障碍(BD = 20)的趋化因子,趋化因子受体,细胞因子和调节性T细胞(T-reg)标志物的免疫基因表达。我们从外周血单个核细胞中提取RNA并进行实时(RT)-PCR以测量趋化因子、趋化因子受体、细胞因子和T-reg标记物的mRNA水平。所有分析均经Bonferroni校正。与HC和SCZ患者相比,BD患者的经典单核细胞活化(M1)标志物il 6、ccl 3显著升高(分别为P = 0.03和P = 0.002; P = 0.024和P = 0.021),而交替(M2)单核细胞活化标志物ccl 1、ccl 22和il 10则一致性降低,(对照组:P = 0.01,P = 0.001和P = 0.09; SCZ受试者:P = 0.02,P = 0.05和P = 0.011)。关于T细胞标志物,BD患者与HC相比下调ccr 5(P = 0.02)和上调il 4(P = 0.04),与健康和SCZ个体相比下调ccl 2(P = 0.006和P = 0.003)和tgf β(分别为P = 0.004和P = 0.007)。在任何免疫基因表达和临床变量(既往住院史、简明精神病评定量表、药物剂量和终生给药)之间均未发现显著相关性。虽然一些标志物由不同的免疫细胞类型表达,但这些发现表明BD患者外周血中M1增加/M2减少的特征具有潜在的Th 1/Th 2偏移。相比之下,所有探索的免疫标志物水平在SCZ中得以保留。需要进一步更大规模的研究来调查BD中炎症反应的相关性,试图将其与精神病理学,治疗和结果测量以及可能的大脑连接相关联。
We here present data on immune gene expression of chemokines, chemokine receptors, cytokines and regulatory T-cell (T-reg) markers in chronic patients suffering from either schizophrenia (SCZ, N = 20) or bipolar disorder (BD = 20) compared with healthy controls (HCs, N = 20). We extracted RNA from peripheral blood mononuclear cells and performed real-time (RT)-PCR to measure mRNA levels of chemokines, chemokine receptors, cytokines and T-reg markers. All the analyses were Bonferroni-corrected. The classical monocyte activation (M1) markers il6, ccl3 were significantly increased in BD as compared with both HC and SCZ patients (P = 0.03 and P = 0.002; P = 0.024 and P = 0.021, respectively), whereas markers of alternative (M2) monocyte activation ccl1, ccl22 and il10 were coherently decreased (controls: P = 0.01, P = 0.001 and P = 0.09; SCZ subjects: P = 0.02, P = 0.05 and P = 0.011, respectively). Concerning T-cell markers, BD patients had compared with HC downregulated ccr5 (P = 0.02) and upregulated il4 (P = 0.04) and compared with both healthy and SCZ individuals downregulated ccl2 (P = 0.006 and P = 0.003) and tgf beta (P = 0.004 and P = 0.007, respectively). No significant associations were found between any immune gene expression and clinical variables (prior hospitalizations, Brief Psychiatric Rating Scale, medications' dosages and lifetime administration). Although some markers are expressed by different immune cell types, these findings suggest a coherent increased M1/decrease M2 signature in the peripheral blood of BD patients with potential Th1/Th2 shift. In contrast, all the explored immune marker levels were preserved in SCZ. Further larger studies are needed to investigate the relevance of inflammatory response in BD, trying to correlate it to psychopathology, treatment and outcome measures and, possibly, to brain connectivity.