Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype.
Enhanced peripheral toll-like receptor responses in psychosis: further evidence of a pro-inflammatory phenotype.
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DOI：
10.1038/tp.2011.37
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发表时间：
2011-08-30
影响因子：
6.8
通讯作者：
Dinan TG
中科院分区：
文献类型：
--
作者：
McKernan DP;Dennison U;Gaszner G;Cryan JF;Dinan TG
低度外周炎症常出现在精神病患者中。Toll样受体（TLR）是启动炎症的模式识别分子。我们的目的是研究精神病患者外周TLR活性。招募了40名精神分裂症患者、20名双相情感障碍患者和40名健康对照（HC）。将捐献的全血与TLR激动剂一起培养24小时。使用多重酶联免疫吸附试验方法分析细胞上清液，以测量IL-1 β、IL-6、IL-8和肿瘤坏死因子-α（TNF α）。分析血浆中的细胞因子、皮质醇和急性期蛋白。在这里，我们发现，选择性TLR激动剂诱导的细胞因子（IL-1 β，IL-6，IL-8和TNF α）的释放增强刺激全血精神分裂症和双相患者相比，HC。与对照组相比，在两种疾病中检测到用TLR2激动剂HKLM治疗后IL-1 β、IL-6和TNF α的过度释放。观察到两种疾病的TLR4诱导的IL-1 β增加增强，双相患者的TNF α增加。检测到两种疾病的TLR8诱导的IL-1 β增加以及双相患者的IL-6和TNF α增加。还观察到精神分裂症患者的TLR9诱导的IL-8增加。未检测到TLR1、TLR3、TLR5、TLR6或TLR7活性的差异。与对照组相比，双相情感障碍患者血浆IL-6水平显著升高，而精神分裂症患者血浆TNF α水平显著升高。双相情感障碍患者血浆急性时相蛋白显著升高。这些数据表明，TLR激动剂介导的细胞因子释放的特异性改变有助于精神障碍中免疫功能障碍的证据。
Low-grade peripheral inflammation is often present in psychotic patients. Toll-like receptors (TLRs) are pattern-recognition molecules that initiate inflammation. Our objective was to investigate the peripheral TLR activity in psychosis. Forty schizophrenia patients, twenty bipolar patients and forty healthy controls (HC) were recruited. Donated whole blood was cultured with TLR agonists for 24 h. Cell supernatants were analysed using a multiplex enzyme-linked immunosorbent assay approach to measure IL-1β, IL-6, IL-8 and tumour necrosis factor-α (TNFα). Plasma was analysed for cytokines, cortisol and acute phase proteins. Here, we show that selective TLR agonist-induced cytokine (IL-1β, IL-6, IL-8 and TNFα) release is enhanced in stimulated whole blood from schizophrenia and bipolar patients compared with HC. An exaggerated release of IL-1β, IL-6 and TNFα following treatment with the TLR2 agonist HKLM was detected in both disorders compared with controls. Enhanced TLR4-induced increases in IL-1β for both disorders coupled with TNFα increases for bipolar patients were observed. TLR8-induced increases in IL-1β for both disorders as well as IL-6 and TNFα increases for bipolar patients were detected. TLR9-induced increases in IL-8 for schizophrenia patients were also observed. No differences in TLR1, TLR3, TLR5, TLR6 or TLR7 activity were detected. Plasma levels of IL-6 were significantly elevated in bipolar patients while TNFα levels were significantly elevated in schizophrenia patients compared with controls. Plasma acute phase proteins were significantly elevated in bipolar patients. These data demonstrate that specific alterations in TLR agonist-mediated cytokine release contribute to the evidence of immune dysfunction in psychotic disorders.
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影响因子：
4.5
作者：
Ellman, Lauren M.;Deicken, Raymond F.;Vinogradov, Sophia;Kremen, William S.;Poole, John H.;Kern, David M.;Tsai, Wei Yann;Schaefer, Catherine A.;Brown, Alan S.
通讯作者：
Brown, Alan S.
DOI：
10.1152/ajpregu.00307.2007
发表时间：
2007-09-01
影响因子：
2.8
作者：
Bailey, Michael T.;Engler, Harald;Sheridan, John F.
通讯作者：
Sheridan, John F.
影响因子：
--
作者：
Merikangas, Kathleen R.;Akiskal, Hagop S.;Kessler, Ronald C.
通讯作者：
Kessler, Ronald C.
影响因子：
10.5
作者：
ADDINGTON, D;ADDINGTON, J;MATICKATYNDALE, E
通讯作者：
MATICKATYNDALE, E
影响因子：
6.6
作者：
Berk, Michael;Ng, Felicity;Tohen, Mauricio
通讯作者：
Tohen, Mauricio