Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?
Fatigue in multiple sclerosis: an example of cytokine mediated sickness behaviour?
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DOI：
10.1136/jnnp.2005.065805
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发表时间：
2006-01-01
影响因子：
11
通讯作者：
Gold, SM
中科院分区：
文献类型：
--
作者：
Heesen, C;Nawrath, L;Gold, SM
背景：疲劳是多发性硬化症（MS）患者的主要主诉。然而，对其病理生理机制知之甚少。慢性疲劳综合征和病态行为研究的证据表明，免疫和神经内分泌因素可能在疲劳的发展中起着致病作用。我们比较了全血刺激能力，（TNF α，IFN γ）和抗炎细胞因子（IL-10）以及下丘脑-垂体-肾上腺（HPA）通过疲劳严重程度量表（fatigue Severity scale，FSS）测定15例有明显疲劳的MS患者和15例无疲劳的MS患者的轴功能。（TNF α：478.9 vs 228.2 pg/ml，p = 0.01; IFN γ：57.6 vs 27.8 pg/ml; p = 0.01）。此外，通过埃普沃思嗜睡量表测量，TNF α值与白天嗜睡显著相关（r = 0.64，p = 0.001）。控制疾病活动性（通过剑桥多发性硬化症基本评分测量）、疾病持续时间、扩展残疾状态量表和抑郁症进一步增加了细胞因子产生和疲劳的相关性。HPA轴的活动是不相关的疲劳，但适度相关的认知impairment.Conclusion：我们的数据表明，疲劳MS至少部分介导的促炎细胞因子的激活。与早期发现一致，HPA轴功能障碍似乎与MS疲劳发病机制无关，但似乎与认知障碍有关。我们的研究结果表明，炎症细胞因子水平的增加可能参与MS疲劳。细胞因子谱的研究可能会增加对MS疲劳发病机制的理解。
Background: Fatigue is a major complaint of multiple sclerosis ( MS) patients. However, little is known about its pathophysiological mechanisms. Evidence from chronic fatigue syndrome and studies on sickness behaviour suggest that immune and neuroendocrine factors may play a causative role in the development of fatigue.Methods: We compared whole blood stimulatory capacity for pro- (TNF alpha, IFN gamma) and anti-inflammatory cytokines (IL-10) as well as hypothalamo-pituitary-adrenal (HPA) axis function in 15 MS patients with marked fatigue and 15 patients without fatigue as determined by the Fatigue Severity Scale (FSS).Results: Proinflammatory cytokines were significantly higher (TNF alpha: 478.9 v 228.2 pg/ml, p = 0.01; IFN gamma: 57.6 v 27.8 pg/ml; p = 0.01) in MS patients with fatigue. Furthermore, TNF alpha values significantly correlated with daytime sleepiness as measured by the Epworth Sleepiness Scale (r = 0.64, p = 0.001). Controlling for disease activity ( as measured by the Cambridge Multiple Sclerosis Basic Score), disease duration, Expanded Disability Status Scale, and depression further increased the correlation of cytokine production and fatigue. HPA axis activity was not related to fatigue but was modestly correlated with cognitive impairment.Conclusion: Our data suggest that fatigue in MS is at least partially mediated through activation of proinflammatory cytokines. In line with earlier findings, HPA axis dysfunction seems not to be relevant in MS fatigue pathogenesis but appears to be linked to cognitive impairment. Our findings suggest that increased levels of inflammatory cytokines may be involved in MS fatigue. Investigation of cytokine profiles may increase the understanding of fatigue pathogenesis in MS.