Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Department of Gastroenterology, Herlev Hospital, University of Copenhagen, Copenhagen, Denmark.
Trends Mol Med. 2017 Apr;23(4):362-374. doi: 10.1016/j.molmed.2017.02.002. Epub 2017 Mar 8.
An unmet medical need exists for the development of targeted therapies for the treatment of inflammatory bowel disease (IBD) with easily administered and stable oral drugs, particularly as most patients on biologics [i.e., tumor necrosis factor (TNF) inhibitors and anti-integrins] are either primary non-responders or lose responsiveness during maintenance treatment. A new class of small molecules, sphingosine-1-phosphate (S1P) receptor modulators, has recently shown efficacy in IBD. Here we provide an overview of the mechanism of action of this novel treatment principle in the context of intestinal inflammation. The remarkable impact of therapeutic modulation of the S1P/S1P receptor axis reflects the complexity of the pathogenesis of IBD and the fact that S1P receptor modulation may be a logical therapeutic approach for the future management of IBD.
目前存在未满足的医学需求，需要开发针对炎症性肠病（IBD）的靶向治疗方法，这些治疗方法最好是易于给药且稳定的口服药物，尤其是因为大多数接受生物制剂[即肿瘤坏死因子（TNF）抑制剂和抗整合素]治疗的患者要么是原发性无应答者，要么在维持治疗期间失去应答。最近，一类新型小分子，即鞘氨醇-1-磷酸（S1P）受体调节剂，在 IBD 中显示出疗效。在这里，我们概述了该新型治疗原理在肠道炎症背景下的作用机制。S1P/S1P 受体轴的治疗调节的显著影响反映了 IBD 发病机制的复杂性，以及 S1P 受体调节可能是未来 IBD 管理的合理治疗方法这一事实。
