摘要
背景:二甲双胍是一种广泛开处方的血糖正常化抗糖尿病药物,由于其抗炎特性,现在开始受到越来越多的关注。 目的:_提供关于二甲双胍对免疫系统和自身炎症疾病影响的现有文献的批判性综合评论。 结果:根据现有的科学文献,二甲双胍主要通过其对各种免疫细胞类型的细胞功能的直接作用,通过诱导AMPK和随后抑制mTORC1,以及通过抑制线粒体ROS产生来抑制免疫应答。在关键的免疫事件中,这导致单核细胞向巨噬细胞分化受到抑制,并抑制活化的巨噬细胞的炎症能力。此外,二甲双胍治疗增加T细胞向调节性和记忆性T细胞的分化,并降低嗜中性粒细胞在NETosis中开始的能力。由于其对免疫细胞促炎表型的抑制作用,二甲双胍似乎不仅减少了几种动物模型中的自身免疫疾病负担,而且在一些人体试验中也显示出有益的结果。 结论:基于其免疫调节特性和作为药物的高耐受性,二甲双胍是用于治疗免疫介导的炎性疾病的未来试验的有趣的附加药物。
关键词: 二甲双胍,炎症,自身免疫疾病,巨噬细胞,T淋巴细胞,嗜中性粒细胞,SLE,RA。
Current Drug Targets
Title:Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?
Volume: 19 Issue: 8
关键词: 二甲双胍,炎症,自身免疫疾病,巨噬细胞,T淋巴细胞,嗜中性粒细胞,SLE,RA。
摘要: Background: Metformin, a widely prescribed blood glucose normalizing antidiabetic drug, is now beginning to receive increasing attention due to its anti-inflammatory properties.
Objective:To provide a critical and comprehensive review of the available literature describing the effects of metformin on the immune system and on auto-inflammatory diseases.
Results:Based on the available scientific literature, metformin suppresses immune responses mainly through its direct effect on the cellular functions of various immune cell types by induction of AMPK and subsequent inhibition of mTORC1, and by inhibition of mitochondrial ROS production. Among key immune events, this results in inhibited monocyte to macrophage differentiation and restrained inflammatory capacity of activated macrophages. In addition, metformin treatment increases differentiation of T cells into both regulatory and memory T cells, as well as decreasing the capacity of neutrophils to commence in NETosis. Due to its inhibitory effect on the proinflammatory phenotype of immune cells, metformin seems to reduce auto-immune disease burden not only in several animal models, but has also shown beneficial results in some human trials.
Conclusions: Based on its immunomodulatory properties and high tolerability as a drug, metformin is an interesting add-on drug for future trials in treatment of immune mediated inflammatory diseases.
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Cite this article as:
Metformin, A New Era for an Old Drug in the Treatment of Immune Mediated Disease?, Current Drug Targets 2018; 19 (8) . https://dx.doi.org/10.2174/1389450118666170613081730
DOI https://dx.doi.org/10.2174/1389450118666170613081730 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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