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首页> 外文期刊>World Journal of Gastroenterology >Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules.
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Novel strategies for the treatment of inflammatory bowel disease: Selective inhibition of cytokines and adhesion molecules.

机译：治疗炎性肠病的新策略：细胞因子和粘附分子的选择性抑制。

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The etiology of inflammatory bowel disease (IBD) has not yet been clarified and immunosuppressive agents which non-specifically reduce inflammation and immunity have been used in the conventional therapies for IBD. Evidence indicates that a dysregulation of mucosal immunity in the gut of IBD causes an overproduction of inflammatory cytokines and trafficking of effector leukocytes into the bowel, thus leading to an uncontrolled intestinal inflammation. Such recent advances in the understanding of the pathogenesis of IBD created a recent trend of novel biological therapies which specifically inhibit the molecules involved in the inflammatory cascade. Major targets for such treatment are inflammatory cytokines and their receptors, and adhesion molecules. A chimeric anti-TNF-alpha monoclonal antibody, infliximab, has become a standard therapy for CD and it is also likely to be beneficial for UC. Several anti-TNF reagents have been developed but most of them seem to not be as efficacious as infliximab. A humanized anti-TNF monoclonal antibody, adalimumab may be useful for the treatment of patients who lost responsiveness or developed intolerance to infliximab. Antibodies against IL-12 p40 and IL-6 receptor could be alternative new anti-cytokine therapies for IBD. Anti-interferon-gamma and anti-CD25 therapies were developed, but the benefit of these agents has not yet been established. The selective blocking of migration of leukocytes into intestine seems to be a nice approach. Antibodies against alpha4 integrin and alpha4beta7 integrin showed benefit for IBD. Antisense oligonucleotide of intercellular adhesion molecule 1 (ICAM-1) may be efficacious for IBD. Clinical trials of such compounds have been either recently reported or are currently underway. In this article, we review the efficacy and safety of such novel biological therapies for IBD.
机译：炎症性肠病（IBD）的病因尚未阐明，并且在IBD的常规疗法中已经使用了非特异性减轻炎症和免疫力的免疫抑制剂。有证据表明，IBD肠道粘膜免疫功能失调会引起炎症细胞因子的过度产生和效应白细胞向肠道的运输，从而导致肠道炎症不受控制。在对IBD的发病机理的理解中的这些最新进展创造了新的生物疗法的新趋势，所述新的生物疗法特异性地抑制了涉及炎症级联的分子。这种治疗的主要靶标是炎性细胞因子及其受体和粘附分子。嵌合的抗TNF-α单克隆抗体英夫利昔单抗已成为CD的标准疗法，它也可能对UC有益。已经开发了几种抗TNF试剂，但大多数似乎不如英夫利昔单抗有效。人源化抗TNF单克隆抗体阿达木单抗可用于治疗对英夫利昔单抗失去反应或发展为不耐受的患者。针对IL-12 p40和IL-6受体的抗体可能是IBD的另一种新的抗细胞因子疗法。已经开发了抗干扰素-γ和抗CD25疗法，但尚未确定这些药物的益处。选择性阻断白细胞向肠道的迁移似乎是一种不错的方法。针对alpha4整合素和alpha4beta7整合素的抗体显示对IBD有好处。细胞间粘附分子1（ICAM-1）的反义寡核苷酸可能对IBD有效。此类化合物的临床试验已被报道或正在进行中。在本文中，我们回顾了这种新型生物疗法对IBD的疗效和安全性。

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