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为什么白介素-10 补充治疗在克罗恩病患者中无效。

Why interleukin-10 supplementation does not work in Crohn's disease patients.

机构信息

Discipline of Nutrition, Faculty of Medical and Health Sciences, The University of Auckland, Auckland 1142, New Zealand.

出版信息

World J Gastroenterol. 2013 Jul 7;19(25):3931-41. doi: 10.3748/wjg.v19.i25.3931.

Abstract

Inflammatory bowel diseases (IBD) such as Crohn's disease (CD) or ulcerative colitis are chronic intestinal disorders, which are on the increase in "Westernised" countries. IBD can be caused by both genetic and environmental factors. Interleukin-10 (IL-10) is an immunoregulatory cytokine that has been identified as being involved in several diseases including IBD. Studies have shown that polymorphisms in the promoter region reduce serum levels of IL-10 and this reduction has been associated with some forms of IBD. Mouse models have shown promising results with IL-10 supplementation, as such IL-10 supplementation has been touted as being a possible alternative treatment for CD in humans. Clinical trials have shown that recombinant human IL-10 is safe and well tolerated up to a dose of 8 μg/kg. However, to date, the results of the clinical trials have been disappointing. Although CD activity was reduced as measured by the CD activity index, IL-10 supplementation did not result in significantly reduced remission rates or clinical improvements when compared to placebo. This review discusses why IL-10 supplementation is not effective in CD patients currently and what can be addressed to potentially make IL-10 supplementation a more viable treatment option in the future. Based on the current research we conclude that IL-10 supplementation is not a one size fits all treatment and if the correct population of patients is chosen then IL-10 supplementation could be of benefit.

摘要

炎症性肠病(IBD),如克罗恩病(CD)或溃疡性结肠炎,是慢性肠道疾病,在“西化”国家呈上升趋势。IBD 可能由遗传和环境因素共同引起。白细胞介素-10(IL-10)是一种免疫调节细胞因子,已被确定与包括 IBD 在内的多种疾病有关。研究表明,启动子区域的多态性降低了血清中 IL-10 的水平,这种降低与某些形式的 IBD 有关。小鼠模型显示出 IL-10 补充的有前景的结果,因此,IL-10 补充被吹捧为人类 CD 的一种可能的替代治疗方法。临床试验表明,重组人 IL-10 在高达 8μg/kg 的剂量下是安全且耐受良好的。然而,迄今为止,临床试验的结果令人失望。尽管 CD 活动根据 CD 活动指数降低,但与安慰剂相比,IL-10 补充并没有导致缓解率或临床改善的显著降低。本文综述讨论了为什么目前 IL-10 补充对 CD 患者无效,以及可以解决哪些问题以使 IL-10 补充成为未来更可行的治疗选择。基于目前的研究,我们得出结论,IL-10 补充不是一种一刀切的治疗方法,如果选择正确的患者人群,IL-10 补充可能会有益。

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