Ogawa Yoshiko, Duru Enrico A, Ameredes Bill T
Section of Immunology, Allergy and Rheumatology, Baylor College of Medicine, Houston, TX, USA.
Curr Mol Med. 2008 Aug;8(5):437-45. doi: 10.2174/156652408785160907.
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-gamma 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-alpha, 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 microg/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.
白细胞介素-10（IL-10）可被视为炎症消退过程中的一种重要介质。它最初因能够抑制Th2细胞中γ干扰素（IFN-γ）和白细胞介素-2（IL-2）的产生而被命名为“细胞因子合成抑制因子”，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（DCs）分泌。单核细胞在受到变应原刺激时，其IL-10的产生和释放会被肿瘤坏死因子-α（TNF-α）上调，并通过自身的负反馈调节实现。然而，它也由调节性T细胞（Tregs）在IL-2的控制下分泌。在哮喘的背景下，重要的是，IL-10通过抑制IL-5和粒细胞-巨噬细胞集落刺激因子（GM-CSF）、直接影响嗜酸性粒细胞凋亡以及通过下调IL-1来影响细胞增殖，从而抑制嗜酸性粒细胞增多。现在认为它的许多细胞因子抑制特性是通过上调细胞因子信号转导抑制因子（SOCS）-3来实现的。IL-10也是一氧化氮（NO）产生的抑制剂，这可能对其在气道炎症性疾病中的作用产生影响。初步临床试验表明，重组人IL-10剂量低于50微克/千克时相对安全，临床不良事件较少，在治疗炎症性肠病和银屑病患者方面取得了不同程度的成功。然而，已知类固醇疗法和变应原特异性免疫疗法都会提高内源性IL-10水平，这可能解释了它们的疗效，这表明有必要进一步研究将IL-10作为治疗哮喘和慢性阻塞性肺疾病（COPD）等气道炎症性疾病的靶点。
