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细胞因子与白塞病。

Cytokines and Behcet's disease.

机构信息

Shanghai Clinical Centre of Rheumatology, Department of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai Institute of Rheumatology, China.

出版信息

Autoimmun Rev. 2012 Aug;11(10):699-704. doi: 10.1016/j.autrev.2011.12.005. Epub 2011 Dec 16.

Abstract

Behcet's Disease (BD) is a systemic vasculitis of unknown etiology. Increasing studies find that a sophisticated interlacing cytokine network is closely implicated in the onset, evolution and even organ damages of the disease. Cytokines involved can be categorized as Th1 type, Th2 type, Th17 type, chemokines and other proinflammatory cytokines, etc. The vicious cycle of cytokine network plays a substantial role in the disease pathogenesis and even in organ lesions, and might be disorganized by blocking one of the key links of the cytokines, which in turn may provide essential clues to outlook the target therapy regimen of cytokine agents in BD. There have been a number of case reports of the positive efficacies of cytokine (and cytokine blocker) agents including Infiximab (Human murine chimeric Anti-TNF α monoclonal antibody), Anakinra (recombinant, non-glycosylated human IL1 receptor antagonist) etc in BD. IFN-α had been used clinically in treating BD with uveitis with beneficial efficacy ever since the 1980s. The studies to date suggested that IL6, IP10 are involved in BD with nervous system lesions, IL17, IL18 are relevant to the superimposed uveitis in patients with BD. Some cytokines i.e. IL8, RANTES, MIP-1α are associated with the disease activity, whereas others are exemplified by that of IL10, whose level shows negative relevance to the disease activity, might be potentially cytokine of protecting effect. According to the related genetic study, the SNPs of numerous cytokines including IL1, TNFα, IFNγ, IL12, and IL18 are pertinent to BD. The recent GWAS (Genome Wide Association Studies) demonstrated that SNPs in the IL10 and IL23R-IL12RB2 region are associated with the disease. Most studies nowadays are confined within the cytokines in the peripheral blood levels, owing to the potentially significant roles of certain cytokines in local lesions. It warrants further in-depth study to address this issue. Moreover, it deserves multi-centre study considering the unique geographical "silk road" display picture of the disease.

摘要

白塞病(BD)是一种病因不明的系统性血管炎。越来越多的研究发现,复杂的细胞因子网络与疾病的发生、发展甚至器官损害密切相关。涉及的细胞因子可分为 Th1 型、Th2 型、Th17 型、趋化因子和其他促炎细胞因子等。细胞因子网络的恶性循环在疾病发病机制甚至器官损伤中起重要作用,通过阻断细胞因子的关键环节之一可能会打乱这种恶性循环,从而为展望 BD 中细胞因子药物的靶向治疗方案提供重要线索。已经有许多关于细胞因子(和细胞因子阻滞剂)药物包括英夫利昔单抗(人鼠嵌合抗 TNFα 单克隆抗体)、阿那白滞素(重组、非糖基化人 IL1 受体拮抗剂)等在 BD 中的阳性疗效的病例报告。自 20 世纪 80 年代以来,IFN-α 已在治疗伴有葡萄膜炎的 BD 中得到临床应用,并取得了有益的疗效。迄今为止的研究表明,IL6、IP10 参与了 BD 伴神经系统病变,IL17、IL18 与 BD 患者重叠性葡萄膜炎有关。一些细胞因子,如 IL8、RANTES、MIP-1α 与疾病活动有关,而其他细胞因子,如 IL10,其水平与疾病活动呈负相关,可能是潜在的保护作用的细胞因子。根据相关的遗传研究,包括 IL1、TNFα、IFNγ、IL12 和 IL18 在内的许多细胞因子的 SNP 与 BD 有关。最近的 GWAS(全基因组关联研究)表明,IL10 和 IL23R-IL12RB2 区域的 SNP 与疾病有关。目前大多数研究都局限于外周血细胞因子水平,因为某些细胞因子在局部病变中可能具有重要作用。这需要进一步深入研究来解决这个问题。此外,考虑到疾病独特的地理“丝绸之路”表现图,这项研究值得多中心研究。

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