Role of IL-10 in the resolution of airway inflammation.
Role of IL-10 in the resolution of airway inflammation.
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DOI：
10.2174/156652408785160907
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发表时间：
2008-08
影响因子：
2.5
通讯作者：
Ameredes BT
中科院分区：
文献类型：
--
作者：
Ogawa Y;Duru EA;Ameredes BT
IL-10可被认为是炎症消退的重要介质。细胞因子合成抑制因子最初被称为细胞因子合成抑制因子，因为它能抑制Th2型细胞中干扰素-γ和IL-2的产生，它由单核细胞、巨噬细胞、肥大细胞、T和B淋巴细胞以及树突状细胞(DC)分泌。单核细胞在过敏反应中产生和释放的IL-10受肿瘤坏死因子-α和自身负反馈调节的上调。然而，它也是由T调节细胞(Tregs)在IL-2的控制下分泌的。重要的是，在哮喘的背景下，IL-10通过抑制IL-5和GM-CSF来抑制嗜酸性粒细胞增多，通过直接作用于嗜酸性粒细胞凋亡，并通过下调IL-1来影响细胞增殖。它的许多细胞因子抑制特性现在被认为是通过上调细胞因子信号转导抑制因子(SOCS)-3而发生的。IL-10也是一氧化氮(NO)产生的抑制因子，这可能与其在呼吸道炎症性疾病中的作用有关。初步临床试验已经证明，重组人IL-10的剂量低于50μg/kg时相对安全，临床不良事件很少，治疗炎症性肠病和牛皮癣患者的效果参差不齐。然而，类固醇治疗和过敏原特异性免疫治疗都能提高内源性IL-10水平，这可能是它们的疗效所在，这表明有必要进一步研究IL-10作为治疗哮喘和COPD等呼吸道炎症性疾病的靶点。
IL-10 can be considered an important agent in the resolution of inflammation. Originally named “cytokine synthesis inhibitory factor” for its ability to inhibit IFN-γ and IL-2 production in Th2 cells, it is secreted by monocytes, macrophages, mast cells, T and B lymphocytes, and dendritic cells (DCs). IL-10 production and release by monocytic cells in response to allergic challenge is upregulated by TNF-α, and by negative feedback regulation of itself. However, it is also secreted by T regulatory cells (Tregs), under the control of IL-2. Importantly in the context of asthma, IL-10 inhibits eosinophilia, by suppression of IL-5 and GM-CSF, by direct effects on eosinophil apoptosis, and effects on cell proliferation through down-regulation of IL-1. A number of its cytokine suppressive characteristics are now thought to occur through its upregulation of suppressor of cytokine signaling (SOCS)-3. IL-10 is also a suppressor of nitric oxide (NO) production, which may have ramifications for its role in airway inflammatory diseases. Initial clinical trials have demonstrated relative safety and few clinically adverse events at doses of recombinant human IL-10 below 50 μg/kg, with mixed success in treatment of patients with inflammatory bowel disease and psoriasis. However, both steroid therapy and allergen specific immunotherapy are known to elevate endogenous IL-10 levels, which may account for their efficacy, suggesting that further study of IL-10 as a target for treatment of airway inflammatory diseases such as asthma and COPD is warranted.
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