Straub Rainer H, Detert Jaqueline, Dziurla René, Fietze Ingo, Loeschmann Peter-Andreas, Burmester Gerd R, Buttgereit Frank
Laboratory of Experimental Rheumatology and Neuroendocrine Immunology, Department of Internal Medicine I, University Hospital, Regensburg, Germany.
Neuroimmunomodulation. 2017;24(1):11-20. doi: 10.1159/000475714. Epub 2017 May 24.
Rheumatoid arthritis (RA) patients have sleep problems, and inflammation influences sleep. We demonstrated that sleep quality improves during intensified treatment with methotrexate (MTX) or etanercept (ETA). Since the hypothalamic-pituitary-adrenal (HPA) axis is involved in sleep regulation, this study investigated the interrelation between sleep parameters, inflammation as objectified by C-reactive protein (CRP), and serum cortisol and adrenocorticotropic hormone (ACTH) levels. Thirty-one eligible patients (disease activity score, DAS28CRP ≥3.2) participated in a 16-week, open, prospective study of HPA axis outcomes. MTX was initiated in 15 patients (female-to-male ratio 9/6) and ETA in 16 patients (14/2). Clinical, laboratory (after polysomnography [PSG] between 8 and 9 a.m.), sleep (PSG), and HPA axis outcome parameters (after PSG between 8 and 9 a.m.) were recorded at baseline and week 16. Clinical characteristics of patients markedly improved throughout the study (e.g., DAS28CRP: p < 0.001; CRP: p < 0.001). Sleep efficiency and wake time after sleep onset markedly improved in the ETA group. Serum cortisol and ACTH did not change during observation. At baseline, serum cortisol levels were negatively correlated to sleep efficiency; this may depend on inflammation, because controlling for CRP eliminated this negative correlation. After ETA treatment, serum cortisol had a high positive correlation with total sleep time, sleep efficiency, and a negative correlation with wake time before and after sleep onset, which was not eliminated by controlling for CRP. In RA patients, the data indicate that inflammation is an important covariate for the crosstalk of sleep and the HPA axis.
类风湿关节炎（RA）患者存在睡眠问题，且炎症会影响睡眠。我们证明，在使用甲氨蝶呤（MTX）或依那西普（ETA）强化治疗期间，睡眠质量会得到改善。由于下丘脑 - 垂体 - 肾上腺（HPA）轴参与睡眠调节，本研究调查了睡眠参数、以C反应蛋白（CRP）为指标的炎症以及血清皮质醇和促肾上腺皮质激素（ACTH）水平之间的相互关系。31名符合条件的患者（疾病活动评分，DAS28CRP≥3.2）参与了一项为期16周的关于HPA轴结果的开放性前瞻性研究。15名患者开始使用MTX（女性与男性比例为9/6），16名患者开始使用ETA（14/2）。在基线和第16周记录临床、实验室指标（上午8点至9点进行多导睡眠图[PSG]检查后）、睡眠指标（PSG）以及HPA轴结果参数（上午8点至9点进行PSG检查后）。在整个研究过程中，患者的临床特征显著改善（例如，DAS28CRP：p < 0.001；CRP：p < 0.001）。ETA组的睡眠效率和睡眠开始后的觉醒时间显著改善。在观察期间，血清皮质醇和ACTH没有变化。在基线时，血清皮质醇水平与睡眠效率呈负相关；这可能取决于炎症，因为控制CRP后消除了这种负相关。ETA治疗后，血清皮质醇与总睡眠时间、睡眠效率呈高度正相关，与睡眠开始前后的觉醒时间呈负相关，控制CRP后这种相关性并未消除。在RA患者中，数据表明炎症是睡眠与HPA轴相互作用的一个重要协变量。
