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白塞病患者血清中的肿瘤坏死因子-α、可溶性白细胞介素-2受体、白细胞介素-6和白细胞介素-8水平升高,且与脂质过氧化增加有关。

Serum levels of TNF-alpha, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behçet's disease.

作者信息

Evereklioglu Cem, Er Hamdi, Türköz Yusuf, Cekmen Mustafa

机构信息

Department of Ophthalmology, Gaziantep University Medical Faculty, Research Hospital, Turkey.

出版信息

Mediators Inflamm. 2002 Apr;11(2):87-93. doi: 10.1080/09629350220131935.

Abstract

AIM

Behçet's disease (BD) is asystemic immunoinflammatory disorder and the aetiopathogenesis is to be specified. Cytokines play a role in immune response and in many inflammatory diseases. The aim of this case-control study is to investigate serum pro-inflammatory cytokine tumour necrosis factor (TNF)-alpha, interleukin-1beta (IL-1beta), soluble IL-2 receptor (sIL-2R), IL-6, and chemokine IL-8 levels in patients with BD. We also determined the end product of lipid peroxidation (malondialdehyde (MDA)) in BD patients as an index for oxidative stress.

METHODS

A total of 37 patients (19 men, 18 women) with BD (active, n = 17; inactive, n = 20) and 20 age-matched and sex-matched healthy control subjects (11 men, nine women) included in this cross-sectional, blinded study. Serum TNF-alpha, IL-1beta, sIL-2R, IL-6 and IL-8 levels were determined by a spectrophotometer technique using the immulite chemiluminescent immunometric assay. Lipid peroxidation was evaluated by Wasowicz et aL The levels of cytokines and lipid peroxidation in the active period were compared with the inactive period of the disease. Results are expressed as mean +/- standard error.

RESULTS

IL-1beta levels were below the detection limits of the assay (< 5 pg/ml) in all samples. Mean levels of MDA (8.1+/-0.7 micromol/l), sIL-2R (800+/-38 U/ml), IL-6 (12.6+/-1.1 pg/ml), IL-8 (7.2+/-0.4 pg/ml), and TNF-alpha (7.9+/-0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (4.3+/-0.5 micromol/l, p < 0.01; 447+/-16 U/ml, p < 0.001; 8.3+/-0.6 pg/ml, p = 0.006; 5.3+/-0.1 pg/ml, p < 0.001; and 5.1 0.2 pg/ml, p < 0.001; respectively) or control subjects (2.1+/-0.2 micromol/l, p < 0.001; 446+/-20 U/ml, p < 0.001; 6.4+/-0.2 pg/ml, p < 0.001; 5.4+/-0.1 pg/ml, p < 0.001; and 4.7+/-0.1 pg/ml, p < 0.001, respectively). On the contrary, only the mean IL-6 level was significantly different between inactive BD and control subjects (p = 0.02). All acute phase reactants were significantly higher in active BD than in inactive period (for each, p < 0.01).

CONCLUSIONS

High levels of sIL-2R, IL-6, IL-8 and TNF-alpha indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-alpha seem to be related to disease activity. Increased lipid peroxidation suggests oxidative stress in BD and therefore tissue damage in such patients. Amelioration of clinical manifestations would be envisaged by targeting these cytokines, chemokines and lipid peroxidation with pharmacological agents.

摘要

目的

白塞病(BD)是一种全身性免疫炎症性疾病,其病因发病机制尚待明确。细胞因子在免疫反应及许多炎症性疾病中发挥作用。本病例对照研究旨在调查BD患者血清促炎细胞因子肿瘤坏死因子(TNF)-α、白细胞介素-1β(IL-1β)、可溶性IL-2受体(sIL-2R)、IL-6和趋化因子IL-8水平。我们还测定了BD患者脂质过氧化的终产物(丙二醛(MDA))作为氧化应激指标。

方法

本横断面、盲法研究纳入了37例BD患者(19例男性,18例女性)(活动期,n = 17;非活动期,n = 20)以及20名年龄和性别匹配的健康对照者(11例男性,9例女性)。采用免疫发光化学免疫分析法,通过分光光度计技术测定血清TNF-α、IL-1β、sIL-2R、IL-6和IL-8水平。脂质过氧化采用Wasowicz等人的方法进行评估。将疾病活动期的细胞因子水平和脂质过氧化水平与非活动期进行比较。结果以平均值±标准误表示。

结果

所有样本中IL-1β水平均低于检测限(<5 pg/ml)。活动期BD患者的MDA(8.1±0.7 μmol/l)、sIL-2R(800±38 U/ml)、IL-6(12.6±1.1 pg/ml)、IL-8(7.2±0.4 pg/ml)和TNF-α(7.9±0.5 pg/ml)平均水平显著高于非活动期患者(分别为4.3±0.5 μmol/l,p<0.01;447±16 U/ml,p<0.001;8.3±0.6 pg/ml,p = 0.006;5.3±0.1 pg/ml,p<0.001;以及5.1±0.2 pg/ml,p<0.001)或对照者(分别为2.1±0.2 μmol/l,p<0.001;446±20 U/ml,p<0.001;6.4±0.2 pg/ml,p<0.001;5.4±0.1 pg/ml,p<0.001;以及4.7±0.1 pg/ml,p<0.001)。相反,仅非活动期BD患者与对照者之间的平均IL-6水平存在显著差异(p = 0.02)。所有急性期反应物在活动期BD患者中均显著高于非活动期(各p<0.01)。

结论

高水平的sIL-2R、IL-6、IL-8和TNF-α表明BD患者免疫系统激活。血清sIL-2R、IL-6、IL-8和TNF-α似乎与疾病活动相关。脂质过氧化增加提示BD患者存在氧化应激,进而导致此类患者组织损伤。通过使用药物靶向这些细胞因子、趋化因子和脂质过氧化,有望改善临床表现。

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