Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities
Inflammatory bowel disease: Epidemiology, pathogenesis, and therapeutic opportunities
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DOI：
10.1097/01.mib.0000195385.19268.68
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发表时间：
2006-01-01
影响因子：
4.9
通讯作者：
Hanauer, SB
中科院分区：
文献类型：
--
作者：
Hanauer, SB
溃疡性结肠炎（UC）和克罗恩病（CD）是炎症性肠病（M）的主要组成部分，由环境、遗传和免疫调节因素的复杂相互作用引起。在北方的工业化国家，IBD的发病率较高，在高加索人和德系犹太人中的患病率较高。种族差距正在缩小，这表明环境因素可能发挥了作用。IBD是多基因的，在某些NOD2变体和CD之间存在最明确的遗传联系。无论潜在的遗传易感性如何，越来越多的数据表明IBD，特别是CD的发病机制中存在对肠道细菌的功能失调的粘膜免疫应答。可能的触发因素包括由特定病原体或病毒感染或粘膜屏障缺陷引起的慢性炎症反应。典型的炎症反应始于中性粒细胞和巨噬细胞的浸润，然后释放趋化因子和细胞因子。这些反过来又加剧了功能失调的免疫应答，并激活肠粘膜中的T（H）1或T（H）2细胞，分别与CD和不太确定的UC相关。免疫学和遗传因素的阐明表明炎症级联反应可能被中断的多个点，从而为IBD提供精确的靶向治疗的可能性。
Ulcerative colitis (UC) and Crohn's disease (CD), the primary constituents of inflammatory bowel disease (M), are precipitated by a complex interaction of environmental, genetic, and immunoregulatory factors. Higher rates of IBD are seen in northern, industrialized countries, with greater prevalence among Caucasians and Ashkenazic Jews. Racial gaps are closing, indicating that environmental factors may play a role. IBD is multigenic, with the most clearly established genetic link between certain NOD2 variants and CD. Regardless of the underlying genetic predisposition, a growing body of data implicates a dysfunctional mucosal immune response to commensal bacteria in the pathogenesis of IBD, especially CD. Possible triggers include a chronic inflammatory response precipitated by infection with a particular pathogen or Virus or a defective mucosal barrier. The characteristic inflammatory response begins with an infiltration of neutrophils and macrophages, which then release chemokines and cytokines. These in turn exacerbate the dysfunctional immune response and activate either T(H)1 or T(H)2 cells in the gut mucosa, respectively associated with CD and, less conclusively, with UC. Elucidation of immunological and genetic factors indicate multiple points at which the inflammatory cascade may be interrupted, yielding the possibility of precise, targeted therapies for IBD.