Proinflammatory cytokines underlying the inflammation of Crohn's disease.
Proinflammatory cytokines underlying the inflammation of Crohn's disease.
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DOI：
10.1097/mog.0b013e328339d099
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发表时间：
2010-07
影响因子：
2.5
通讯作者：
Fichtner-Feigl S
中科院分区：
文献类型：
--
作者：
Strober W;Zhang F;Kitani A;Fuss I;Fichtner-Feigl S
本综述的目的是概括我们目前对克罗恩病炎症相关促炎细胞因子的理解，以及利用这些信息基于对这些细胞因子的抑制来为该疾病设计治疗方法的前景。
当前的研究为Th1和Th17反应在克罗恩病发病机制中的作用提供了新的见解。十年前进行的初步研究强调了这样一种观点，即克罗恩病炎症是由白细胞介素 - 12（IL - 12）驱动的Th1反应引起的，这种反应导致干扰素 - γ（IFN - γ）的产生，而干扰素 - γ随后成为主要的炎症介质。然而，近年来，这种观点在很大程度上被主要在小鼠模型中进行的研究所掩盖，这些研究表明Th17反应通过产生白细胞介素 - 17（IL - 17）是克罗恩病炎症的主要原因。现在，一种更为平衡的观点正在出现，即干扰素 - γ在克罗恩病中仍然是一种主要的促炎细胞因子，尽管它可能在炎症过程的不同阶段由Th1和Th17细胞介导的反应产生。
新的研究结果继续支持这样一种观点，即抗白细胞介素 - 12p40（一种抑制Th1和Th17反应的抗体）从逻辑上讲是治疗克罗恩病最有效的抗细胞因子药物。
The purpose of this review is to encapsulate our current understanding of the pro-inflammatory cytokines responsible for the inflammation underlying Crohn’s disease and the prospect of using this information to devise therapy for this condition based on inhibition of these cytokines. Current research is shedding new light on the role of both Th1 and Th17 responses in the pathogenesis of Crohn’s disease. Initial studies conducted a decade ago highlighted the view that Crohn’s disease inflammation is caused by an IL-12-driven Th1 response which resulted in the generation of IFN-γ which then served as the main inflammatory mediator. In recent years, however, this view has been largely eclipsed by studies, conducted mainly in murine models, showing that a Th17 response is the main cause of Crohn’s disease inflammation through the production of IL-17. Now, a somewhat more balance view is emerging which holds that IFN-γ is still a major pro-inflammatory cytokine in Crohn’s disease although it may arise from both the Th1 and Th17 cell-mediated responses at different phases of the inflammatory process. The new findings continue to support the idea that anti-IL-12p40, an antibody that inhibits both the Th1 and Th17 response, is logically the most potent anti-cytokine for the treatment of Crohn’s disease.