Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome.
Reduction of Glucocorticoid Receptor Function in Chronic Fatigue Syndrome.
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DOI：
10.1155/2018/3972104
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发表时间：
2018
影响因子：
4.6
通讯作者：
Watson S
中科院分区：
文献类型：
--
作者：
Lynn M;Maclachlan L;Finkelmeyer A;Clark J;Locke J;Todryk S;Ng WF;Newton JL;Watson S
糖皮质激素受体（GR）的功能可能在慢性疲劳综合征（CFS）中具有病原病理学意义，通过其在介导炎症反应以及下丘脑-垂体-肾上腺轴调节中的重要作用。GR功能可以通过测量地塞米松（指数）调节细胞因子对脂多糖（LPS）的反应来估计，在体内通过指数对皮质醇水平的影响来估计。本研究旨在比较CFS （n = 48）、原发性Sjögren’s综合征（疾病组对照）（n = 27）和久坐健康对照（hc） （n = 20）的GR功能，并探讨其与临床指标的关系。在GR体外反应实验中，全血被稀释后用LPS孵育（以刺激细胞因子的产生），有或没有10或100纳摩尔浓度的dex。流式细胞术和细胞头阵列（CBA）可以定量上清液中细胞因子（TNFα、白细胞介素- (IL-) 6和IL-10）的水平。在体内反应试验中，连续两个早晨，每隔半小时取5份血浆样本，用ELISA法测定总皮质醇浓度，在晚上11点摄入0.5 mg dex。体内和体外分析的数据与报告的童年逆境的关联也进行了检查。与两个对照组相比，CFS患者lps诱导的IL-6和tnf - α的产生减少，与hcc相比，高剂量的dex降低了tnf - α的抑制。皮质醇水平，在指数之前或之后，CFS和hc之间没有差异。与hc相比，CFS患者的皮质醇水平变化更大。在联合组（CFS + HC）中，皮质醇浓度和体外GR功能（由指数介导的IL-10抑制决定）与童年逆境评分呈正相关。结果不支持GR失调在CFS中是病因性的假设，并提示当前和未来CFS的内分泌横断面研究可能容易受到儿童期创伤的混杂影响，而儿童期创伤可能因共病抑郁症而增加。
Glucocorticoid receptor (GR) function may have aetiopathogenic significance in chronic fatigue syndrome (CFS), via its essential role in mediating inflammatory responses as well as in hypothalamic-pituitary-adrenal axis regulation. GR function can be estimated ex vivo by measuring dexamethasone (dex) modulation of cytokine response to lipopolysaccharide (LPS), and in vivo using the impact of dex on cortisol levels. This study aimed to compare the GR function between CFS (n = 48), primary Sjögren's syndrome (a disease group control) (n = 27), and sedentary healthy controls (HCs) (n = 20), and to investigate its relationship with clinical measures. In the GR ex vivo response assay, whole blood was diluted and incubated with LPS (to stimulate cytokine production), with or without 10 or 100 nanomolar concentrations of dex. Cytometric bead array (CBA) and flow cytometry enabled quantification of cytokine levels (TNFα, interleukin- (IL-) 6, and IL-10) in the supernatants. In the in vivo response assay, five plasma samples were taken for determination of total cortisol concentration using ELISA at half-hourly intervals on two consecutive mornings separated by ingestion of 0.5 mg of dex at 11 pm. The association of the data from the in vivo and ex vivo analyses with reported childhood adversity was also examined. CFS patients had reduced LPS-induced IL-6 and TNFα production compared to both control groups and reduced suppression of TNFα by the higher dose of dex compared to HCs. Cortisol levels, before or after dex, did not differ between CFS and HCs. Cortisol levels were more variable in CFS than HCs. In the combined group (CFS plus HC), cortisol concentrations positively and ex vivo GR function (determined by dex-mediated suppression of IL-10) negatively correlated with childhood adversity score. The results do not support the hypothesis that GR dysregulation is aetiopathogenic in CFS and suggest that current and future endocrine cross-sectional studies in CFS may be vulnerable to the confounding influence of childhood trauma which is likely increased by comorbid depression.
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影响因子：
4.1
作者：
Kruschke, John K.
通讯作者：
Kruschke, John K.
影响因子：
13.6
作者：
Lorusso, Lorenzo;Mikhaylova, Svetlana V.;Ricevuti, Giovanni
通讯作者：
Ricevuti, Giovanni
影响因子：
4.8
作者：
Bernstein, DP;Stein, JA;Zule, W
通讯作者：
Zule, W
影响因子：
5.6
作者：
Carvalho, L. A.;Garner, B. A.;Dew, T.;Fazakerley, H.;Pariante, C. M.
通讯作者：
Pariante, C. M.
DOI：
10.1093/occmed/kqp180
发表时间：
2010-03-01
期刊：
Occupational medicine (Oxford, England)
影响因子：
--
作者：
Frith, James;Newton, Julia
通讯作者：
Newton, Julia