Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases.
Proinflammatory cytokines in the pathogenesis of inflammatory bowel diseases.
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DOI：
10.1053/j.gastro.2011.02.016
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发表时间：
2011-05
期刊：
影响因子：
29.4
通讯作者：
Fuss IJ
中科院分区：
文献类型：
--
作者：
Strober W;Fuss IJ
炎症性肠病（IBD）的细胞因子反应是决定炎症发生、发展和最终消退的关键病理生理因素。过去20年的研究现在提供了这些反应的性质的详细（但还不完整）图片。第一层细胞因子应答由主导疾病的T细胞分化模式控制。因此，在克罗恩病中，主要的细胞因子来自Th1和Th17 CD4 + T细胞分化，并且由这些类型的分化产生的IFN-γ和IL-17/IL-22组成。这些细胞因子对克罗恩氏炎症的相对重要性尚不清楚，尽管越来越多的证据表明IFN-γ是最重要的（同类中的第一）。相反，在溃疡性结肠炎中，Th2样分化过程是最重要的，其导致产生IL-13（和可能的IL-5）的NKT细胞的扩增。这些疾病特异性细胞因子模式产生第二层细胞因子，其跨越Th1/Th17-Th2分裂并充当炎症的上游促进剂和下游介质。这些细胞因子包括众所周知的TNF-α、IL-1 β、IL-6三酸盐以及最近研究的称为TL1A的细胞因子。在这篇综述中，我们将探讨这一细胞因子景观提供了一个了解如何最近和未来的抗细胞因子疗法的实际功能。
The cytokine responses characterizing the inflammatory bowel diseases (IBDs) are the key pathophysiologic elements that govern the initiation, evolution and, ultimately, the resolution of these forms of inflammation. Studies over the last two decades now provide a detailed (but not yet complete) picture of the nature of these responses. The first tier of cytokine responses are governed by the T cell differentiation patterns dominating the disease. Thus, in Crohn’s disease, the major cytokines arise from Th1 and Th17 CD4+ T cell differentiation and consist of IFN-γ and IL-17/IL-22 generated by these types of differentiation. The relative importance of these cytokines to Crohn’s inflammation is still unclear, although evidence is mounting that IFN-γ is primus inter pare (first among equals). In contrast, in ulcerative colitis a Th2-like differentiation process is paramount which results in the expansion of NKT cells producing IL-13 (and perhaps IL-5). These disease-specific cytokine patterns give rise to a second tier of cytokines that span the Th1/Th17–Th2 divide and act as upstream facilitators and downstream mediators of inflammation. These cytokines include the well-known TNF-α, IL-1β, IL-6 triumphirate as well as a more recently studied cytokine known as TL1A. In this review, we will explore this cytokine landscape with the view of providing an understanding of how recent and future anti-cytokine therapies actually function.
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