Cholinergic anti-inflammatory pathway activity and high mobility group box-1 (HMGB1) serum levels in patients with rheumatoid arthritis
Cholinergic anti-inflammatory pathway activity and high mobility group box-1 (HMGB1) serum levels in patients with rheumatoid arthritis
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DOI：
10.2119/2006-00108.goldstein
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发表时间：
2007-03-01
影响因子：
5.7
通讯作者：
Tracey, Kevin J.
中科院分区：
文献类型：
--
作者：
Goldstein, Richard S.;Bruchfeld, Annette;Tracey, Kevin J.
高迁移率族蛋白-1(HMGB1)是一种细胞因子，与类风湿关节炎(RA)和其他炎症性疾病的发病机制有关。胆碱能抗炎途径是一种迷走神经依赖机制，在实验性疾病模型中抑制HMGB1的释放。在这里，我们研究类风湿性关节炎患者迷走神经活性与HMGB1的关系。我们比较了13名RA患者和11名年龄和性别匹配的对照组的RR间期变异性、HMGB1和hsCRP血清水平以及疾病活动评分。RA患者血清HMGB1和hsCRP水平明显高于对照组(HMGB1=71 ng/mL45~99对18 ng/mL0~40，P<0.0001；hsCRP=14.5 mg/L对1 mg/L，P<0.001)。RA患者RR间期变异性显著低于对照组(HF=38msec(2)(14-80)vs.288msec(2)(38-364)，P<；0.0001；rMSSID=20.9+/-9.79msec，52.6+/-35.3msec，P<；0.01)。HMGB1水平与RR间期变异性显著相关(Rho=-0，49，P<；0.01)。RA患者血清HMGB1水平与疾病活动性评分(DAS-28)显著相关(P=0.004)。这项研究设计不能确定因果关系，但结果与假设一致，即RA患者胆碱能抗炎途径活性降低与HMGB1水平升高有关。
High Mobility Group Box-1 (HMGB1) is a cytokine implicated in the pathogenesis of rheumatoid arthritis (RA) and other inflammatory diseases. The cholinergic anti-inflammatory pathway, a vagus nerve-dependent mechanism, inhibits HMGB1 release in experimental disease models. Here, we examine the relationship between vagus nerve activity and HMGB1 in patients with RA. We compared RR interval variability, an index of cardiac vagal modulation, HMGB1 and hsCRP serum levels, and disease activity scores in thirteen RA patients and eleven age- and sex-matched controls. In RA patients, serum levels of HMGB1 and hsCRP were elevated as compared with controls (HMGB1 = 71 ng/mL (45-99) vs. 18 ng/mL (0-40), P < 0.0001; hsCRP = 14.5 mg/L (0.7-59) vs. I mg/L (0.4-2.9), P < 0.001). RR interval variability in RA patients was significantly decreased as compared with controls (HF = 38 msec(2) (14-80) vs. 288 msec(2) (38-364), P < 0.0001; rMSSID = 20.9 +/- 9.79 msec, 52.6 +/- 35.3 msec, P < 0.01). HMGB1 levels and RR interval variability were significantly related (rho = -0,49, P < 0.01). HMGB1 serum levels significantly correlated with disease activity scores (DAS-28) in patients with RA (P = 0.004). The study design does not enable a determination of causality, but the results are consistent with the hypothesis that decreased cholinergic anti-inflammatory pathway activity is associated with increased HMGB1 levels in patients with RA.