Sabry Alaa, Sheashaa Hussein, El-Husseini Amr, Mahmoud Khaleed, Eldahshan Khaleed F, George Shahir K, Abdel-Khalek Ehab, El-Shafey E M, Abo-Zenah Hamdy
Nephrology and Internal medicine department, Mansoura Urology and Nephrology Center, Mansoura University, Egypt.
Cytokine. 2006 Aug;35(3-4):148-53. doi: 10.1016/j.cyto.2006.07.023. Epub 2006 Oct 5.
Systemic Lupus Erythematosus (SLE) is an autoimmune disease characterized by a wide variety of autoantibodies, some of which are pathogenic. In recent years it has become more evident that the polyclonal B cell activation in SLE is T-cell dependent. The stimulation of the autoantibody producing B cells is likely mediated by the TH2 subtype of T cells producing IL-4, IL-5, IL-6 and IL- 10, whereas the TH1 subtype secreting IL-2 and IFN-gamma predominates in cell-mediated immune response. Tumor Necrosis Factor (TNF-alpha) is both a proinflammatory and an immunoregulatory cytokine. TNF-alpha has differential effects on B cells, on T cells and on dendritic cells as well as on the process of programmed cell death. Understanding how the immune system integrates the pleiotropic properties of TNF-alpha is a challenge, particularly so in diseases like SLE. Meanwhile the role of IL-6 in the pathogenesis of SLE is controversial.
To investigate whether serum levels of TNF-alpha and IL-6 is higher in Egyptian patients with SLE than healthy control volunteers and its correlation with the clinical activity in patients with different activity scores as measured by Systemic Lupus Erythmatosus Disease Activity Index (SLEADI).
Sixty individuals (40 patients with Systemic lupus Erythmatosus and 20 healthy control volunteers) were the subject of this study, they were subjected to thorough clinical examination, laboratory investigations, their clinical disease activity was scored according to SLEDAI, and serum sampling was obtained for TNF-alpha and IL-6 levels assay. Renal biopsy was carried out and examined by light microscopy by a pathologist blinded with the clinical activity.
The mean level of TNF-alpha was (766.95+/-357.82Pg/ml) for patients with active disease while it was (314.01+/-100.87Pg/ml) for those with inactive disease and (172.7+/-39.19Pg/ml) for the healthy control group. The difference was statistically significant (P=.002). The mean level of IL-6 was (135.4+/-54.23Pg/ml) for patients with active disease while it was (47.33+/-18.61Pg/ml) for those with inactive disease and (21.15+/-10.99Pg/ml) for the healthy control group. The difference was statistically significant (P=.002). A significant correlations between TNF-alpha and IL-6 serum levels and the SLEDAI score was observed (r=.743 and .772, respectively).
Serum TNF-alpha and IL-6 are sensitive markers of SLE disease activity. They may be useful independent markers for prediction of SLE disease activity and to differentiate normal subjects from those having SLE. Possible therapeutic implications in the treatment of SLE in the future deserve wide scale trials.
系统性红斑狼疮（SLE）是一种自身免疫性疾病，其特征是存在多种自身抗体，其中一些具有致病性。近年来，越来越明显的是，SLE中的多克隆B细胞活化是T细胞依赖性的。产生自身抗体的B细胞的刺激可能由产生IL-4、IL-5、IL-6和IL-10的T细胞的TH2亚型介导，而分泌IL-2和IFN-γ的TH1亚型在细胞介导的免疫反应中占主导地位。肿瘤坏死因子（TNF-α）既是一种促炎细胞因子，也是一种免疫调节细胞因子。TNF-α对B细胞、T细胞、树突状细胞以及程序性细胞死亡过程具有不同的作用。了解免疫系统如何整合TNF-α的多效性特性是一项挑战，在SLE等疾病中尤其如此。同时，IL-6在SLE发病机制中的作用存在争议。
研究埃及SLE患者血清TNF-α和IL-6水平是否高于健康对照志愿者，以及它们与通过系统性红斑狼疮疾病活动指数（SLEADI）测量的不同活动评分患者的临床活动的相关性。
本研究的对象为60人（40例系统性红斑狼疮患者和20名健康对照志愿者），他们接受了全面的临床检查、实验室检查，根据SLEDAI对其临床疾病活动进行评分，并采集血清样本检测TNF-α和IL-6水平。进行肾活检，并由对临床活动不知情的病理学家通过光学显微镜检查。
活动期疾病患者的TNF-α平均水平为（766.95±357.82Pg/ml），非活动期疾病患者为（314.01±100.87Pg/ml），健康对照组为（172.7±39.19Pg/ml）。差异具有统计学意义（P = 0.002）。活动期疾病患者的IL-6平均水平为（135.4±54.23Pg/ml），非活动期疾病患者为（47.33±18.61Pg/ml），健康对照组为（21.15±10.99Pg/ml）。差异具有统计学意义（P = 0.002）。观察到TNF-α和IL-6血清水平与SLEDAI评分之间存在显著相关性（分别为r = 0.743和0.772）。
血清TNF-α和IL-6是SLE疾病活动的敏感标志物。它们可能是预测SLE疾病活动以及区分正常人与SLE患者的有用独立标志物。未来在SLE治疗中的潜在治疗意义值得进行大规模试验。
