Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients
Activation of cytokines corroborate with development of inflammation and autoimmunity in thromboangiitis obliterans patients
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DOI：
10.1111/j.1365-2249.2012.04624.x
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发表时间：
2012-10-01
影响因子：
4.6
通讯作者：
Evora, P. R. B.
中科院分区：
文献类型：
--
作者：
Dellalibera-Joviliano, R.;Joviliano, E. E.;Evora, P. R. B.
血栓闭塞性脉管炎（TAO）是一种节段性炎症闭塞性疾病，影响年轻吸烟者的手臂和腿部动脉。免疫系统似乎在TAO的病因学中起着关键作用;然而，对血管组织炎症进展所涉及的方面以及因此对该疾病的演变的了解仍然有限。本研究旨在研究具有急性临床表现的TAO患者血浆中肿瘤坏死因子（TNF）-α、白细胞介素（IL）-1 β、IL-4、IL-17和IL-23的细胞因子水平。该研究纳入了20例接受临床随访的年龄为38 - 59岁的TAO患者（n = 10例女性; n = 10例男性），分为两组：（i）TAO既往吸烟者（n = 11）和（ii）TAO主动吸烟者（n = 9）;对照组包括正常志愿者非吸烟者（n = 10）、主动吸烟者（n = 10）和既往吸烟者（n = 10）。采用夹心酶联免疫吸附试验测定患者血浆样本。使用非参数MannWhitney U-检验进行统计分析，参数显著性为P < 0.05。TAO患者组与正常对照组相比，所有细胞因子的活性均不同，对照组吸烟者的细胞因子活性降低。与对照组相比，TAO患者中TNF-α、IL-1 β、IL-4、IL-17和IL-23水平的增加是显著的（P < 0.005，所有参数）。本文提供的结果表明TAO中细胞因子的产生增加，可能有助于在患者血管水平观察到的炎症反应。此外，IL-17和IL-23水平的升高提示TAO的紊乱与自身免疫机制有关。因此，IL-17的发现及其与炎症和自身免疫病理学的关联重塑了我们关于TAO发病机制的观点，TAO的发病机制以前基于T辅助细胞1型（Th 1）Th 2范例。
Thromboangiitis obliterans (TAO) is a segmental inflammatory occlusive disorder that affects the arm and leg arteries of young smokers. The immune system seems to play a critical role in the aetiology of TAO; however, knowledge of the aspects involved in the progression of vascular tissue inflammation and, consequently, the evolution of this disease is still limited. This study was carried out to investigate the cytokine levels of tumour necrosis factor (TNF)-a, interleukin (IL)-1 beta, IL-4, IL-17 and IL-23 in the plasma of TAO patients presenting with acute clinical manifestations. The study included 20 TAO patients (n = 10 women; n = 10 men) aged 3859 years under clinical follow-up, classified into two groups: (i) TAO former smokers (n = 11) and (ii) TAO active smokers (n = 9); the control groups included normal volunteer non-smokers (n = 10, active smokers (n = 10) and former smokers (n = 10). Patients' plasma samples were measured using the sandwich enzyme-linked immunosorbent assay. Statistical analyses were performed using the non-parametric MannWhitney U-test, with parameters significant at P < 0.05. The activities of all cytokines were different in groups of TAO patients when compared with normal controls, and decreased for control smokers. Increased levels of TNF-a, IL-1 beta, IL-4, IL-17 and IL-23 were significant in patients with TAO when compared to the controls (P < 0.005, all parameters). The results presented here indicate an increased production of cytokines in TAO, possibly contributing to the inflammatory response observed in the patients' vascular levels. In addition, the increased levels of IL-17 and IL-23 suggest that the disturbance of TAO is involved with mechanisms of autoimmunity. Thus, the discovery of IL-17 and its association with inflammation and autoimmune pathology has reshaped our viewpoint regarding the pathogenesis of TAO, which was based previously on the T helper type 1 (Th1)Th2 paradigm.