CROHNS-DISEASE - A PERMEABILITY DISORDER OF THE TIGHT JUNCTION
CROHNS-DISEASE - A PERMEABILITY DISORDER OF THE TIGHT JUNCTION
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DOI：
10.1136/gut.29.12.1621
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发表时间：
1988-12-01
期刊：
影响因子：
24.5
通讯作者：
HOLLANDER, D
中科院分区：
文献类型：
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作者：
HOLLANDER, D
尽管做了大量的努力，克罗恩病的病因仍未确定。研究集中在可能的感染或免疫原因上，但尚未对该病的发病机制提供明确的解释。许多传染因子如细菌、病毒、支原体和分枝杆菌被认为可能引起克罗恩病。1-3到目前为止，没有一种传染因子符合科赫的假设，也没有一种传染因子一直被证实是这种疾病的致病因子。可能的免疫异常也已被研究。许多研究者都在寻找原发免疫异常或免疫反应异常。同样，这些努力都没有一致地确定免疫异常是克罗恩病的原因。在克罗恩病的病因研究中，前列腺素代谢最近受到了广泛的关注。许多研究人员已经能够证明，在克罗恩病患者的炎症结肠粘膜或结肠管内容物中，PGE2浓度升高。“其他类前列腺素1213和白三烯含量增加”在克罗恩病患者中也有报道。目前的共识是，克罗恩病中前列腺素代谢的变化可能是继发于炎症过程本身，而不是潜在的病因学因素。虽然克罗恩病的病因和发病机制很复杂，但我认为通过异常紧密连接增加肠道通透性可能起作用。我并不是说肠通透性增加是克罗恩病发展的唯一病因；相反，我认为肠道渗透性的增加可能会使抗原或感染性因子渗透到肠壁中，从而开始在易感个体中最终导致克罗恩病的过程。增加肠道渗透性可能很重要的提议并不新鲜。然而，最近新的临床和实验证据足以表明，应该认真考虑将这一建议作为一种可行的假设。
Despite extensive efforts the aetiology of Crohn's disease hasyet to be established. Studies have concentrated on possible infectious or immunological causes, but have not provided a clear explanation of the pathogenesis of this disease. Many infectious agents such as bacteria, viruses, mycoplasma, and mycobacteria have been considered as possibly causing Crohn's disease. 1-3 So far none of the infectious agents have fulfilled Koch's postulates or beenconsistently confirmed as a causative agent of this disease. Possible immunological abnormalities have also been studied. 4 Numerous investigators have looked for either primary immunological abnormalities5 or abnormalities of immune response. 6 Again, none of these efforts have consistently identified immunological abnormalities as the cause of Crohn's disease. 78 Prostanoid metabolism has recently received extensive scrutiny in the search for the aetiology of Crohn's disease. Numerous investigators have been able to show increased PGE2 concentrations in inflamed colonic mucosa9'or colonic lumenal contents from patients with Crohn's disease.'1 Increased elaboration of other prostanoids9 1213 and leucotrienes"has also been reported in patients with Crohn's disease. The consensus of opinion is that changes in prostanoid metabolism in Crohn's disease are probably secondary to the inflammatory process itself and not an underlying aetio-logical factor. 14While the aetiology and pathogenesis of Crohn's disease is complex, I propose that increased intestinal permeability through abnormal tight junctions could play a role. I am not proposing that increased intestinal permeability is the only aetiological factor in the development of Crohn's disease; rather, I am proposing thatincreased intestinal permeability could allow the penetration of antigenic or infectious agents into the intestinal wall and thus start the process which in susceptible individuals culminates in Crohn's disease. The proposal that increased intestinal permeability could be important is not new.'5 Recent new clinical and experimental evidence,'" 2'however, is sufficient to suggestserious consideration of this proposal as a working hypothesis.