Serum levels of TNF-α, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behcet's disease
Serum levels of TNF-α, sIL-2R, IL-6, and IL-8 are increased and associated with elevated lipid peroxidation in patients with Behcet's disease
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DOI：
10.1080/09629350220131935
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发表时间：
2002-04-01
影响因子：
4.6
通讯作者：
Çekmen, M
中科院分区：
文献类型：
--
作者：
Evereklioglu, C;Er, H;Çekmen, M
目的：白塞病（BD）是一种全身性免疫炎性疾病，其发病机制有待明确。细胞因子在免疫反应和许多炎症性疾病中发挥作用。本病例对照研究的目的是研究BD患者血清促炎细胞因子肿瘤坏死因子(TNF)- α、白细胞介素-1 β (il -1 β)、可溶性IL-2受体（sIL-2R）、IL-6和趋化因子IL-8的水平。我们还测定了BD患者脂质过氧化终产物（丙二醛（MDA））作为氧化应激的指标。方法：本横断面盲法研究共纳入37例BD患者（男性19例，女性18例）（活动期17例，非活动期20例）和20例年龄匹配、性别匹配的健康对照（男性11例，女性9例）。血清tnf - α、il -1 β、sIL-2R、IL-6和IL-8水平采用免疫荧光法测定。脂质过氧化由Wasowicz等人评估。将活跃期与非活跃期的细胞因子和脂质过氧化水平进行比较。结果表示为平均值+/-标准误差。结果：所有样品中il -1 β水平均低于检测限（< 5 pg/ml）。意思是MDA水平(8.1 + / - 0.7μmol / l), sIL-2R (800 + / - 38 U /毫升),il - 6 (12.6 + / - 1.1 pg / ml),引发(7.2 + / - 0.4 pg / ml),和肿瘤坏死因子-α(7.9 + / - 0.5 pg / ml)在活跃BD患者明显高于那些不活跃的患者(4.3 + / - 0.5μmol / l, p < 0.01; 447 + / - 16 U /毫升,p < 0.001; 8.3 + / - 0.6 pg / ml, p = 0.006; 5.3 + / - 0.1 pg / ml p < 0.001; 5.1 + / - 0.2 pg / ml, p < 0.001;分别)和对照组(2.1 + / - 0.2μmol / l, p < 0.001; 446 + / - 20 U /毫升,p < 0.001;6.4 +/- 0.2 pg/ml, p < 0.001；5.4 +/- 0.1 pg/ml, p < 0.001；4.7 +/- 0.1 pg/ml, p < 0.001)。相反，只有IL-6水平在非活性BD组与对照组之间有显著差异（p = 0.02）。活性BD急性期各反应物均显著高于非活性BD （p < 0.01）。结论：高水平的il - 2r、IL-6、IL-8和TNF-α提示BD患者免疫系统激活，血清il - 2r、IL-6、IL-8和TNF-α可能与疾病活动性有关。脂质过氧化水平升高提示双相障碍患者存在氧化应激，从而导致组织损伤。改善临床表现将设想通过靶向这些细胞因子，趋化因子和脂质过氧化的药物。
AIM Behcet's disease (BD) is a systemic 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 μmol/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-α (7.9 +/- 0.5 pg/ml) in active BD patients were significantly higher than those in inactive patients (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; and 5.1 +/- 0.2 pg/ml, p < 0.001; respectively) or control subjects (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; 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-α indicate the activation of immune system in BD. Serum sIL-2R, IL-6, IL-8 and TNF-α 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.