内皮素-1及特定细胞因子在与系统性结缔组织病相关的雷诺现象发病机制中的作用。

The role of endothelin-1 and selected cytokines in the pathogenesis of Raynaud's phenomenon associated with systemic connective tissue diseases.

作者信息

Rychlik-Golema W, Mastej K, Adamiec R

机构信息

Department and Clinic of Angiology, Hypertension and Diabetology, Medical University of Wroclaw, Wroclaw, Poland.

出版信息

Int Angiol. 2006 Jun;25(2):221-7.

PMID:16763543

Abstract

AIM

In the pathogenesis of Raynaud's phenomenon humoral and immunoinflammatory agents are involved. The aim of this study was the assessment of the level of endothelin-1 (ET-1), tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), soluble IL-6 receptor (IL-6sR), von Willebrand's factor (vWF) and platelet factor 4 (PF-4) in patients with Raynaud's phenomenon associated with systemic connective tissue diseases.

METHODS

The examined group consisted of 32 patients (24 women and 8 men) with Raynaud's phenomenon associated with selected connective tissue diseases, aged 28-50 years. A control group consisted of 13 healthy volunteers. Immediately after a cold provocation test venous blood was taken in order to assess serum concentrations of: TNF-alpha, IL-6, IL-6sR, vWF, PF-4, antinuclear antibodies (ANA), antineutrophil antibodies (c-ANCA).

RESULTS

In the group of patients with Raynaud's phenomenon mean serum concentration of ET-1, TNF-alpha, PF-4, and vWF was significantly greater than in the healthy group. In contrast, serum IL-6 and IL-6sR concentrations did not differ significantly between the diseased and healthy groups. In a subgroup of Raynaud's phenomenon patients showing particularly high concentration of serum ET-1 (twice as much as mean control concentration), the increase in IL-6, IL-6sR, vWF and c-ANCA concentration exhibited statistical significance in comparison with patients with lower serum ET-1 concentration. The vWF concentration exhibited positive correlation with time interval between the occurrence of clinical symptoms and serum ANA antibodies concentration. The increase in ET-1 synthesis in Raynaud's phenomenon patients is dependent on the increase in IL-6 level and c-ANCA antibodies level.

CONCLUSIONS

The patients with Raynaud's phenomenon show an increase in ET-1 and TNF-alpha concentrations. An enhanced ET-1 synthesis is dependent on the augmentation of serum c-ANCA antibodies and IL-6 concentrations.

摘要

目的

在雷诺现象的发病机制中涉及体液和免疫炎症介质。本研究的目的是评估与系统性结缔组织疾病相关的雷诺现象患者体内内皮素-1（ET-1）、肿瘤坏死因子（TNF-α）、白细胞介素-6（IL-6）、可溶性IL-6受体（IL-6sR）、血管性血友病因子（vWF）和血小板因子4（PF-4）的水平。

方法

研究组由32例（24例女性和8例男性）与特定结缔组织疾病相关的雷诺现象患者组成，年龄在28至50岁之间。对照组由13名健康志愿者组成。在冷激发试验后立即采集静脉血，以评估血清中TNF-α、IL-6、IL-6sR、vWF、PF-4、抗核抗体（ANA）、抗中性粒细胞抗体（c-ANCA）的浓度。

结果

雷诺现象患者组中ET-1、TNF-α、PF-4和vWF的平均血清浓度显著高于健康组。相比之下，患病组和健康组之间血清IL-6和IL-6sR浓度无显著差异。在血清ET-1浓度特别高（是平均对照浓度的两倍）的雷诺现象患者亚组中，与血清ET-1浓度较低的患者相比，IL-6、IL-6sR、vWF和c-ANCA浓度的升高具有统计学意义。vWF浓度与临床症状出现与血清ANA抗体浓度之间的时间间隔呈正相关。雷诺现象患者中ET-1合成的增加依赖于IL-6水平和c-ANCA抗体水平的升高。