Department of Gastroenterology, Medical Section, Herlev Hospital, University of Copenhagen , Copenhagen , Denmark.
Front Med (Lausanne). 2014 Mar 24;1:3. doi: 10.3389/fmed.2014.00003. eCollection 2014.
The etiology of inflammatory bowel disease (IBD), of which ulcerative colitis (UC) and Crohn's disease (CD) are the two most prevailing entities, is unknown. However, IBD is characterized by an imbalanced synthesis of pro-inflammatory mediators of the inflamed intestine, and for more than a decade tumor necrosis factor-(TNF) α has been a major target for monoclonal antibody therapy. However, TNF inhibitors are not useful for one third of all patients (i.e. "primary failures"), and further one third lose effect over time ("secondary failures"). Therefore, other strategies have in later years been developed including monoclonal antibodies targeting the interleukin (IL)-6 family of receptors (the p40 subunit of IL-12/IL-23) as well as monoclonal antibodies inhibiting adhesion molecules (the α4β7 heterodimers), which direct leukocytes to the intestinal mucosa. Recently, small molecules, which are inhibitors of Janus kinases (JAKs), hold promise with a tolerable safety profile and efficacy in UC, and the field of nanomedicine is emerging with siRNAs loaded into polyactide nanoparticles that may silence gene transcripts at sites of intestinal inflammation. Thus, drug development for IBD holds great promise, and patients as well as their treating physicians can be hopeful for the future.
炎症性肠病（IBD）的病因尚不清楚，其中溃疡性结肠炎（UC）和克罗恩病（CD）是两种最常见的疾病。然而，IBD 的特征是炎症肠道中促炎介质的不平衡合成，十多年来，肿瘤坏死因子-α（TNF）一直是单克隆抗体治疗的主要靶点。然而，TNF 抑制剂对三分之一的所有患者（即“原发性失败”）没有作用，而且进一步的三分之一随着时间的推移失去效果（“继发性失败”）。因此，近年来开发了其他策略，包括针对白细胞介素（IL）-6 受体家族的单克隆抗体（IL-12/IL-23 的 p40 亚单位）以及抑制黏附分子的单克隆抗体（α4β7 异二聚体），这些抗体将白细胞引导至肠黏膜。最近，Janus 激酶（JAK）抑制剂小分子在 UC 中具有良好的安全性和疗效，纳米医学领域也在不断涌现，将 siRNA 装载到聚乳酸纳米颗粒中可能会在肠道炎症部位沉默基因转录本。因此，IBD 的药物开发前景广阔，患者及其治疗医生对未来充满希望。
