Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity.
Role of pro- and anti-inflammatory phenomena in the physiopathology of type 2 diabetes and obesity.
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DOI：
10.4331/wjbc.v8.i2.120
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发表时间：
2017-05-26
期刊：
影响因子：
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通讯作者：
Ferraz JC
中科院分区：
文献类型：
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作者：
Pirola L;Ferraz JC
在肥胖症中，持续的低度炎症被认为是导致胰岛素抵抗和2型糖尿病进展的主要因素，而在瘦受试者中，免疫环境是非炎症性的。随着肥胖症的发展，促炎性M1巨噬细胞和几种T细胞亚群的大量脂肪组织（AT）浸润导致大量促炎性细胞因子（包括白细胞介素-1 β（IL-1β）、肿瘤坏死因子α、IL-17和IL-6）在AT和全身蓄积，这些细胞因子与肥胖表型向代谢综合征的进展密切相关。同时，抗炎M2巨噬细胞和产生抗炎细胞因子IL-10、IL-5和干扰素-γ的Th亚群（包括Th 2和T-reg细胞）与瘦个体中AT稳态的维持相关。在这里，我们讨论的基本原则，在控制AT和浸润免疫细胞之间的相互作用，在精益和肥胖的条件下，特别强调促炎和抗炎细胞因子的贡献，建立胰岛素抵抗状态。在这种情况下，我们将讨论目前的知识水平的改变，促炎和抗炎细胞因子在肥胖，胰岛素抵抗和2型糖尿病，在人类和动物模型。最后，我们还简要地调查了最近的新的治疗策略，试图减轻或逆转胰岛素抵抗和2型糖尿病通过管理的重组抑制性抗体针对一些促炎细胞因子。
In obesity, persistent low-grade inflammation is considered as a major contributor towards the progression to insulin resistance and type 2 diabetes while in lean subjects the immune environment is non-inflammatory. Massive adipose tissue (AT) infiltration by pro-inflammatory M1 macrophages and several T cell subsets as obesity develops leads to the accumulation - both in the AT and systemically - of numerous pro-inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor α, IL-17 and IL-6 which are strongly associated with the progression of the obese phenotype towards the metabolic syndrome. At the same time, anti-inflammatory M2 macrophages and Th subsets producing the anti-inflammatory cytokines IL-10, IL-5 and interferon-γ, including Th2 and T-reg cells are correlated to the maintenance of AT homeostasis in lean individuals. Here, we discuss the basic principles in the control of the interaction between the AT and infiltrating immune cells both in the lean and the obese condition with a special emphasis on the contribution of pro- and anti-inflammatory cytokines to the establishment of the insulin-resistant state. In this context, we will discuss the current knowledge about alterations in the levels on pro- and anti-inflammatory cytokines in obesity, insulin resistance and type 2 diabetes mellitus, in humans and animal models. Finally, we also briefly survey the recent novel therapeutic strategies that attempt to alleviate or reverse insulin resistance and type 2 diabetes via the administration of recombinant inhibitory antibodies directed towards some pro-inflammatory cytokines.