Crohn's disease (CD) and ulcerative colitis (UC) are chronic inflammatory disorders of the gastrointestinal tract that share clinical and pathological characteristics. The most accredited hypothesis is that both CD and UC result from a deregulated mucosal immune response to normal constituents of the gut microflora. Evidence, however, indicates that the main pathological processes in these two diseases are distinct. In CD, the tissue-damaging inflammatory reaction is driven by activated type 1 helper T-cell (Th1), whereas a humoral response predominates in UC. Consistently, a marked accumulation of macrophages making interleukin (IL)-12, the major Th1-inducing factor, is seen in CD but not in UC mucosa. Preliminary studies also indicate that administration of a monoclonal antibody blocking the IL-12/p40 subunit can be useful to induce and maintain clinical remission in CD patients. Notably, the recently described IL-23 shares the p40 subunit with IL-12, raising the possibility that the clinical benefit of the anti-IL-12/p40 antibody in CD may also be due to the neutralization of IL-23 activity. This review summarizes the current information on the expression and functional role of IL-12 and IL-12-associated signaling pathways both in patients with CD and experimental models of colitis, thus emphasizing major differences between IL-12 and IL-23 activity on the development of intestinal inflammation.

译文

克罗恩病 (CD) 和溃疡性结肠炎 (UC) 是胃肠道的慢性炎症性疾病,具有共同的临床和病理特征。最受认可的假设是,CD和UC都是由于对肠道微生物群落正常成分的粘膜免疫反应失调所致。然而,有证据表明,这两种疾病的主要病理过程是不同的。在CD中,破坏组织的炎症反应是由激活的1型辅助T细胞 (Th1) 驱动的,而在UC中,体液反应占主导地位。一致地,在CD中观察到产生主要Th1-inducing因子白介素 (IL)-12的巨噬细胞的明显积累,但在UC粘膜中未见。初步研究还表明,施用阻断IL-12/p40亚基的单克隆抗体可用于诱导和维持CD患者的临床缓解。值得注意的是,最近描述的IL-23与IL-12共享p40亚基,这增加了CD中anti-IL-12/p40抗体的临床益处也可能归因于IL-23活性的中和的可能性。这篇综述总结了有关CD患者和结肠炎实验模型中IL-12和IL-12-associated信号通路的表达和功能作用的最新信息,从而强调了IL-12和IL-23活性在肠道炎症发展中的主要差异。

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