克罗恩病(CD)和溃疡性结肠炎(UC)是以肠道炎症为特征的炎症性肠病(IBD)。促炎细胞因子肿瘤坏死因子-α(TNF-α)的肠道水平升高与疾病的活动性和严重程度有关。在IBD的治疗中全身有效地施用抗TNF-α疗法。然而,全身暴露与可能阻碍治疗性治疗的不良事件相关.临床研究表明,功效与胃肠道(GIT)中的免疫作用相关,而不是全身作用。这些数据表明,IBD中的位点特异性TNF-α抑制可能是有效的,与全身暴露相关的预期副作用较少。因此,我们回顾了研究局部TNF-α抑制在IBD中的功效或可行性的现有文献。使用给定的搜索词和策略在PubMed上进行了文献检索。在8739次点击中,这篇综述包括48篇引文。这些研究范围从动物研究到随机安慰剂对照临床试验。在这些研究中,局部抗TNF-α治疗是用抗体实现的,反义寡核苷酸(ASO),小干扰RNA(siRNA),microRNA(miRNA)和转基因生物。鉴于IBD中局部TNF-α抑制的临床相关性,这篇叙述性综述总结并讨论了这些方法。
Crohn\'s disease (CD) and ulcerative colitis (UC) are inflammatory bowel diseases (IBD) characterized by intestinal inflammation. Increased intestinal levels of the proinflammatory cytokine tumor necrosis factor-α (TNF-α) are associated with disease activity and severity. Anti-TNF-α therapy is administered systemically and efficacious in the treatment of IBD. However, systemic exposure is associated with adverse events that may impede therapeutic treatment. Clinical studies show that the efficacy correlates with immunological effects localized in the gastrointestinal tract (GIT) as opposed to systemic effects. These data suggest that site-specific TNF-α inhibition in IBD may be efficacious with fewer expected side effects related to systemic exposure. We therefore reviewed the available literature that investigated the efficacy or feasibility of local TNF-α inhibition in IBD. A literature search was performed on PubMed with given search terms and strategy. Of 8739 hits, 48 citations were included in this
review. These studies ranged from animal studies to randomized placebo-controlled clinical trials. In these studies, local anti-TNF-α therapy was achieved with antibodies,
antisense oligonucleotides (ASO), small interfering RNA (siRNA), microRNA (miRNA) and genetically modified organisms. This narrative
review summarizes and discusses these approaches in view of the clinical relevance of local TNF-α inhibition in IBD.