Malik Talha, Mannon Peter
Division of Gastroenterology/Hepatology, University of Alabama at Birmingham, Birmingham, Alabama 35924, USA.
Front Biosci (Schol Ed). 2012 Jan 1;4(3):1172-89. doi: 10.2741/s324.
An enormous amount of pathoetiologic information continues to accrue from animal models of inflammatory bowel disease and study of the gut microbiome that is providing expanded insight into the causes and mechanisms of inflammatory bowel diseases. This knowledge is being translated into new therapeutics that are being tested in Crohn's and ulcerative colitis patients with an aim to enhance treatment responses by moving away from immunosuppression and toward immunomodulation. In the last decade, the frontier of emerging IBD therapy has been dominated by biological agents that specifically target pro-inflammatory cytokines most notably tumor necrosis factor-alpha. However, it is clear that the gaps in therapy (primary and secondary non-response and the potential for drug side effects and intolerances) continue. To fill these gaps, various approaches are being employed to develop novel strategies, from inhibiting additional pro-inflammatory cytokines to focusing on blocking inflammatory cell trafficking, decreasing inflammatory cell mass, enhancing regulatory cell function and reinforcing epithelial barrier function. To these ends, aggressive and innovative research is being pursued to develop more robust treatment strategies and identify key molecular targets.
从炎症性肠病的动物模型以及肠道微生物群研究中不断积累了大量病理病因学信息，这些研究为深入了解炎症性肠病的病因和机制提供了更多见解。这些知识正转化为新的治疗方法，并在克罗恩病和溃疡性结肠炎患者中进行测试，旨在通过从免疫抑制转向免疫调节来提高治疗反应。在过去十年中，新兴的炎症性肠病治疗前沿一直由特异性靶向促炎细胞因子（最显著的是肿瘤坏死因子-α）的生物制剂主导。然而，治疗方面的差距（原发性和继发性无反应以及药物副作用和不耐受的可能性）依然存在。为了填补这些差距，人们采用了各种方法来制定新策略，从抑制其他促炎细胞因子到专注于阻断炎症细胞运输、减少炎症细胞数量、增强调节细胞功能以及加强上皮屏障功能。为此，人们正在积极开展创新性研究，以制定更有效的治疗策略并确定关键分子靶点。
