Korzenik J R, Dieckgraefe B K
Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
Dig Dis Sci. 2000 Jun;45(6):1121-9. doi: 10.1023/a:1005541700805.
The current hypothesis for the etiology of Crohn's disease proposes an excessive immune response, largely T-cell driven, possibly against endogenous bacteria. Standard therapy is therefore directed towards suppression of this immune response. An alternative theory of pathogenesis accounts for epidemiologic and pathophysiologic observations that have been hitherto underemphasized, namely, (1) genetic disorders with deficiencies in neutrophil function can give rise to a clinical and pathologic syndrome indistinguishable from Crohn's; (2) abnormal neutrophil function is well described in Crohn's disease; (3) a group of bacteria implicated in other chronic inflammatory disorders causes impairment of neutrophil function; and (4) 20th century environmental risk factors for Crohn's disease may directly suppress neutrophil function and may have led to a shift in the dominant gut flora with similar effects. We propose that some cases of Crohn's disease result from the interaction of environmental and genetic influences leading to impaired mucosal neutrophil function, resulting in failure to effectively clear intramucosal microbes effectively. While encompassing existing data, this hypothesis proposes a proximate defect in the mucosal immune response. If this paradigm were correct, new therapeutic approaches might involve strategies to alter intestinal flora and stimulate neutrophil function.
目前关于克罗恩病病因的假说认为，其发病机制是一种过度的免疫反应，主要由T细胞驱动，可能是针对内源性细菌。因此，标准治疗方法旨在抑制这种免疫反应。另一种发病机制理论解释了一些迄今为止未被充分重视的流行病学和病理生理学观察结果，即：（1）中性粒细胞功能缺陷的遗传性疾病可引发一种在临床和病理上与克罗恩病无法区分的综合征；（2）在克罗恩病中，中性粒细胞功能异常已有详细描述；（3）一组与其他慢性炎症性疾病相关的细菌可导致中性粒细胞功能受损；（4）20世纪克罗恩病的环境危险因素可能直接抑制中性粒细胞功能，并可能导致优势肠道菌群发生变化，产生类似影响。我们认为，某些克罗恩病病例是环境和遗传因素相互作用导致黏膜中性粒细胞功能受损的结果，从而无法有效清除黏膜内的微生物。该假说在涵盖现有数据的同时，提出了黏膜免疫反应中的一个直接缺陷。如果这一范例正确，新的治疗方法可能涉及改变肠道菌群和刺激中性粒细胞功能的策略。
