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首页> 外文期刊>Current medicinal chemistry-Anti-inflammatory & anti-allergy agents.Anti-inflammatory & anti-allergy agents >Biologic and Novel Therapy of the Inflammatory Bowel Diseases
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Biologic and Novel Therapy of the Inflammatory Bowel Diseases

机译：生物和小说治疗炎症肠道疾病

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摘要

IBD is now best considered as a group of genetic disorders of immune dysregulation with failure of down-regulation of the intestinal mucosa's normal immune response to its intraluminal commensal bacterial milieu combined with inappropriate migration of antigenic material triggered by multiple host (appendectomy, pregnancy, breast feeding, age) and environmental factors (tobacco smoking, birth control pill, NSAIDS). The result is the predominance of an effector or pro-inflammatory cytokine response due to clonal expansion of TI and T_2 helper lymphocytes (Th| and Th_2 response) combined with an inadequate regulatory cytokine response by T_3 helper (Th3) and T] regulatory (Tri) lymphocytes. The persistence of this imbalance in the inflammatory response then leads to tissue damage resulting in both local and systemic illness. In human IBD, a distinction can now be drawn between Crohn's disease with its Th] effector response characterized by high levels of the cytokines interleukin-12 (IL-12), interferon gamma (IFN(gamma)) and tumor necrosis factor (TNF) leading to transmural inflammation with granulomas, and ulcerative colitis with a Th_2 effector response, high levels of interleukin-4 (IL-4), interleukin-5 (IL-5), interleukin-6 (IL-6), and interleukin-13 (IL-13) characterized by strictly mucosal inflammation. The difficulty with adherence to current maintenance therapy for the inflammatory bowel diseases as well as the toxicity and relative ineffectiveness of induction therapy has provided the impetus for the development of new biologic and novel therapies which will be reviewed in this article.Biologic therapy has been divided into five areas of study: 1) native biologic preparations and isolates such as vaccines, hormone fragments and blood products, 2) recombinant peptides or proteins, including granulocyte macrophage colony stimulating factor, 3) monoclonal antibody-based therapies, 4) anti-sense nucleotides to nucleic acids, and 5) cell and gene therapies Since the early 1990's, investigation in all five of these areas has yielded numerous potential agents for use in treating IBD more effectively and safely. While only one, infliximab (Remicade), is PDA-approved, several additional agents should be available for clinical us6 In the near future with the promise of more to follow. Our discussion of biologic and novel therapies represents a review of the most promising treatments and a status report of on-going clinical trials. Peripheral leukocyte apheresis and stem cell transplants, while suggesting an exciting new pathway for investigation, will not be reviewed. Our discussion is organized by each agent's hypothesized mode of intervention in altering the pathogenesis of IBD.
机译：炎症性肠病是现在最好的视为一组基因疾病的免疫失调的失败肠粘膜的下调是正常的免疫反应的管腔内的共生体细菌环境结合不合适移植抗原物质引发的多个主机(阑尾切除术、怀孕、乳房喂,年龄)和环境因素(烟草吸烟、避孕药、非甾体抗炎药)。的优势是一个效应或吗由于克隆促炎细胞因子的反应TI的扩张和T_2辅助淋巴细胞(Th |和Th_2响应)加上一个不足调节细胞因子反应T_3助手(Th3)和T]监管(三)淋巴细胞。坚持这种不平衡的炎症反应会导致组织损伤导致本地和系统性疾病。克罗恩氏之间的区别现在可以了疾病与Th)效应的反应特点是高水平的细胞因子interleukin-12 (il - 12)、干扰素γ(干扰素(γ))和肿瘤坏死因子(TNF)导致透壁的炎症Th_2肉芽肿,溃疡性结肠炎效应响应,高水平的interleukin-4(il - 6)和interleukin-13 (IL-13)特征通过严格的粘膜炎症。坚持目前的维持治疗炎症性肠病的毒性和相对无效诱导治疗提供了动力新的生物和小说的发展治疗了篇文章。五个方面的研究:1)原生生物准备和隔离等疫苗,激素碎片和血液制品,2)重组多肽或蛋白质,包括粒细胞巨噬细胞集落刺激因子,3)单克隆抗体类治疗,4)核酸反义核苷酸,5)自1990年代早期细胞和基因疗法,五个方面的调查产生了许多潜在的代理使用治疗IBD更有效和安全。只有一个,英夫利昔单抗(Remicade) PDA-approved,几个额外的代理应该是可用的在不久的将来临床us6与承诺更多的遵循。新的治疗方法代表了一个审查的最有前途的治疗和状态报告正在进行的临床试验。apheresis和干细胞移植,而提出一个令人兴奋的新途径调查,不会了。讨论是由每个代理假设模式改变的干预炎症性肠病的发病机制。

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