Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome
Proinflammatory cytokines and autoimmunity in Churg-Strauss syndrome
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DOI：
10.1196/annals.1361.053
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发表时间：
2005-01-01
期刊：
影响因子：
--
通讯作者：
Gross, WL
中科院分区：
文献类型：
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作者：
Hellmich, B;Csernok, E;Gross, WL
Churg-Strauss综合征（CSS）属于抗神经细胞胞浆抗体（ANCA）相关性血管炎，其进一步特征是严重的嗜酸性粒细胞增多症，通常为肉芽肿性炎症。重组干扰素-α（IFN-α）和肿瘤坏死因子-α（TNF-α）阻断的治疗效果指向细胞因子在CSS发病机制中的中心作用。最近的数据表明，与其他原发性系统性血管炎相比，外周血单核细胞（PBMC）不仅分泌大量的1型辅助性T细胞（Th 1）细胞因子，特别是IFN-γ，而且还释放2型辅助性T细胞因子，如白细胞介素-4（IL-4）和白细胞介素-13（IL-13）。白细胞介素-5是嗜酸性粒细胞产生和成熟嗜酸性粒细胞（CSS中的关键效应细胞）的功能活化的最有效刺激剂。所呈现的数据显示，与健康对照相比，来自用T细胞特异性刺激物培养的CSS患者的PBMC分泌显著增加量的IL-5，表明IL-5实质上有助于CSS中嗜酸性粒细胞增多的发展。由于重组IFN-α在体外下调CD 4（+）T细胞的IL-5产生，CSS患者中IL-5分泌增加可能为重组IFN-α在疾病中的治疗功效提供线索。在不同的疾病阶段，Th 1和Th 2细胞因子之间的平衡变化可能有助于CSS患者的不同临床病程，其范围可以从突出的Th 1介导的全身性血管炎和肉芽肿性炎症的一端到Th 2介导的系统性嗜酸性粒细胞增多症的另一端。虽然ANCA与CSS的关联指向疾病的自身免疫起源，但目前还没有直接证据表明ANCA在CSS中的直接致病作用。
Churg-Strauss syndrome (CSS) belongs to the antineutrophil cytoplasmic antibody (ANCA)-associated vasculitides and is further characterized by severe eosinophilia and, often, granulomatous inflammation. The therapeutic efficacy of recombinant interferon-alpha (IFN-alpha) and tumor necrosis factor-alpha (TNF-alpha) blockade point toward a central role of cytokines in the pathogenesis of CSS. Recent data show that, in contrast to other primary systemic vasculitides, peripheral blood mononuclear cells (PBMCs) secrete not only large amounts of T helper type 1 (Th1) cytokines, particulary IFN-gamma, but also release T helper type 2 (Th2) cytokines such as interleukin-4 (IL-4) and interleukin-13 (IL-13). Interleukin-5 is the most potent stimulator of eosinophil production and functional activation of mature eosinophils, the key effector cells in CSS. Data are presented showing that PBMCs from patients with CSS cultured with T cell-specific stimuli secrete significantly increased amounts of IL-5 compared with healthy controls, suggesting that IL-5 contributes substantially to the development of eosinophilia in CSS. As recombinant IFN-alpha downregulates IL-5 production of CD4(+) T cells in vitro, the increased secretion of IL-5 in patients with CSS may provide the clue for the therapeutic efficacy of recombinant IFN-alpha in the disease. Variations in the balance between Th1 and Th2 cytokines at different disease stages could contribute to the distinct clinical courses seen in patients with CSS, which can range from prominent Th1-mediated generalized vasculitis and granulomatous inflammation on one end of the spectrum to Th2-mediated systemic hypereosinophilia on the other. Although the association of ANCAs with CSS point toward an autoimmune origin of the disease, there is no direct evidence as yet for a direct pathogenic role of ANCAs in CSS.