Andrews Caroline, McLean Mairi H, Durum Scott K
*Cancer and Inflammation Program, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Frederick, Maryland; and †School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen, United Kingdom.
Inflamm Bowel Dis. 2016 Sep;22(9):2255-64. doi: 10.1097/MIB.0000000000000818.
Inflammatory bowel disease (IBD) is an inflammatory disorder of the intestine that affects an estimated 329 per 100,000 people in the United States and is increasing in incidence within a number of cultures worldwide. Likely due to its incompletely understood pathophysiology and etiology, the standard treatments for IBD are only efficacious in subsets of patients and often do not induce lasting remission. As a result, novel therapies are needed. The success of anti-tumor necrosis factor-α treatment in a subset of patients with IBD demonstrated that therapy targeting a single cytokine could be efficacious in IBD, and clinical trials investigating the blockade of a variety of cytokines have commenced. Interleukin (IL) 27 is a relatively recently discovered type I cytokine with established roles in infectious disease, autoimmunity, and cancer in a variety of organs. IL-27 was identified as a candidate gene for IBD, and a number of studies in mouse models of IBD have demonstrated that IL-27 therapy is protective. However, in contrast to these investigations, genetic deletion of the IL-27 receptor has been shown to be protective in some mouse models of IBD. The purpose of this review is to highlight the recent literature investigating the role of IL-27 in IBD and to discuss the possible explanations for the sometimes conflicting results of these studies. Evidence supporting IL-27 therapy as a treatment for IBD will also be discussed.
炎症性肠病(IBD)是一种肠道炎症性疾病,在美国每10万人中估计有329人受其影响,并且在全球许多文化背景下其发病率都在上升。可能由于其病理生理学和病因尚未完全了解,IBD的标准治疗仅对部分患者有效,且往往无法诱导持久缓解。因此,需要新的治疗方法。抗肿瘤坏死因子-α治疗在一部分IBD患者中取得成功,表明针对单一细胞因子的治疗在IBD中可能有效,并且已经开始了研究多种细胞因子阻断作用的临床试验。白细胞介素(IL)-27是一种相对较新发现的I型细胞因子,在多种器官的传染病、自身免疫和癌症中发挥着既定作用。IL-27被确定为IBD的候选基因,并且在IBD小鼠模型中的多项研究表明IL-27治疗具有保护作用。然而,与这些研究相反,在一些IBD小鼠模型中,IL-27受体的基因缺失已被证明具有保护作用。本综述的目的是强调最近研究IL-27在IBD中作用的文献,并讨论这些研究有时出现相互矛盾结果的可能原因。还将讨论支持IL-27治疗作为IBD治疗方法的证据。