ter Wolbeek Maike, van Doornen Lorenz J P, Schedlowski Manfred, Janssen Onno E, Kavelaars Annemieke, Heijnen Cobi J
Laboratory of Psychoneuroimmunology, University Medical Center Utrecht, The Netherlands.
Psychoneuroendocrinology. 2008 Apr;33(3):375-85. doi: 10.1016/j.psyneuen.2007.12.005. Epub 2008 Jan 31.
Fatigue during adolescence is associated with somatic and psychological complaints that resemble the pattern of symptoms described for chronic fatigue syndrome (CFS). Studies in CFS and other stress-related syndromes suggested a dysfunction of the interactions between the hypothalamic-pituitary-adrenal axis (HPA-axis) and the immune system, i.e. a changed glucocorticoid (GC) receptor sensitivity of immune cells, to exist. Here we investigated whether severely fatigued girls from a healthy population have altered cortisol production and immune cell sensitivity for the synthetic GC, dexamethasone (DEX). In a longitudinal design, we examined ex vivo DEX sensitivity of monocytes and of T-cell mitogen-induced responses of severely fatigued (N=65) and non-fatigued girls (N=60). Fatigued girls reported more severe comorbid complaints than non-fatigued participants across three measurements during 1 year (T1: spring, T2: autumn, T3: spring) and had higher plasma cortisol levels throughout the study. DEX sensitivity of T-cell mitogen-induced responses showed seasonal variation with increased sensitivity in autumn compared to spring. No systematic variation of monocyte glucocorticoid receptor (GR) sensitivity was observed. Significant rank correlations of DEX sensitivity of T-cell mitogen-induced responses between the three assessments during the year suggest a stable trait of immune function. Groups did not differ in DEX sensitivity on any of the read outs. However, in a persistently fatigued subgroup, sensitivity to DEX was significantly reduced on the level of interferon (IFN)-gamma production. These results show that although fatigued participants had severe (comorbid) complaints, only in the case when symptoms persisted, altered GC sensitivity of immune cells was observed.
青春期的疲劳与一些躯体和心理不适有关，这些不适类似于慢性疲劳综合征（CFS）所描述的症状模式。对CFS和其他与压力相关综合征的研究表明，下丘脑-垂体-肾上腺轴（HPA轴）与免疫系统之间的相互作用存在功能障碍，即免疫细胞的糖皮质激素（GC）受体敏感性发生了改变。在此，我们调查了来自健康人群的严重疲劳女孩是否存在皮质醇分泌改变以及免疫细胞对合成GC地塞米松（DEX）的敏感性变化。在一项纵向研究中，我们检测了严重疲劳女孩（N = 65）和非疲劳女孩（N = 60）的单核细胞对DEX的体外敏感性以及T细胞有丝分裂原诱导反应。在1年中的三次测量（T1：春季，T2：秋季，T3：春季）中，疲劳女孩报告的共病不适比非疲劳参与者更严重，并且在整个研究过程中血浆皮质醇水平更高。T细胞有丝分裂原诱导反应的DEX敏感性呈现季节性变化，秋季的敏感性高于春季。未观察到单核细胞糖皮质激素受体（GR）敏感性的系统性变化。一年中三次评估之间T细胞有丝分裂原诱导反应的DEX敏感性存在显著的等级相关性，表明免疫功能具有稳定的特征。两组在任何一项检测指标上的DEX敏感性均无差异。然而，在持续疲劳的亚组中，干扰素（IFN）-γ产生水平对DEX的敏感性显著降低。这些结果表明，尽管疲劳参与者有严重的（共病）不适，但只有在症状持续的情况下，才观察到免疫细胞的GC敏感性改变。
