Zhao B, Zhang S, Chen W, Zhang R, Jiang R, Zhang R, Chen L
Department of Ophthalmology and Vision Science, the Eye & ENT Hospital, Shanghai Medical College, Fudan University, Shanghai 200031, China.
Key Laboratory of Myopia of State Health Ministry (Fudan University) and Shanghai Key Laboratory of Visual Impairment and Restoration, Shanghai 200031, China.
Curr Mol Med. 2018 Mar 9;17(7):460-467. doi: 10.2174/1566524018666180207152941.
BACKGROUND & OBJECTIVE: Interleukin 37 (IL-37) is an important regulator of the anti-inflammatory T-cell response. In this study, we investigated its expression and function in peripheral blood mononuclear cells (PBMCs) of patients with HLA-B27 associated acute anterior uveitis (AAU) and idiopathic AAU.
15 patients with HLA-B27-associated AAU, 10 patients with idiopathic AAU and 22 controls were recruited to this study from August 2013 to December 2016. Complete ophthalmological examinations were performed and clinical features were clearly documented. Blood samples were collected and peripheral blood mononuclear cells were extracted. IL-37 messenger RNA (mRNA) and protein expression in peripheral blood mononuclear cells (PBMCs) were examined by performing RT-PCRs and western blot, respectively. Cytokines in the supernatants of stimulated dendritic cells (DCs) with IL-37 were assayed by multiplex immunoassay.
An increased level of IL-37 mRNA and protein expression by PBMCs was found in the patient group with clinically active AAU compared to controls. There was no significant difference in IL-37 mRNA and protein expression levels between HLA-B27 associated AAU and idiopathic AAU. IL-37 significantly inhibited the production of IL-1β, IL-6, IL-10, IL-21, IL-23, TNF-α and IFN-γ. IL-37 levels of mRNA and protein expression showed a significant positive correlation with disease activity.
Elevated IL-37 expression is associated with disease activity in HLA-B27 associated AAU and idiopathic AAU. IL-37 can inhibit proinflammatory cytokine productions in AAU. Manipulation of IL-37 may offer a new therapeutic target for these entities.
白细胞介素37（IL-37）是抗炎性T细胞反应的重要调节因子。在本研究中，我们调查了其在HLA-B27相关急性前葡萄膜炎（AAU）和特发性AAU患者外周血单个核细胞（PBMC）中的表达及功能。
2013年8月至2016年12月，招募了15例HLA-B27相关AAU患者、10例特发性AAU患者和22例对照者纳入本研究。进行了全面的眼科检查，并详细记录了临床特征。采集血样并提取外周血单个核细胞。分别通过逆转录聚合酶链反应（RT-PCR）和蛋白质印迹法检测外周血单个核细胞（PBMC）中IL-37信使核糖核酸（mRNA）和蛋白表达。通过多重免疫测定法检测用IL-37刺激的树突状细胞（DC）上清液中的细胞因子。
与对照组相比，临床活动期AAU患者组中PBMC的IL-37 mRNA和蛋白表达水平升高。HLA-B27相关AAU和特发性AAU之间的IL-37 mRNA和蛋白表达水平无显著差异。IL-37显著抑制IL-1β、IL-6、IL-10、IL-21、IL-23、肿瘤坏死因子-α（TNF-α）和干扰素-γ（IFN-γ）的产生。IL-37的mRNA和蛋白表达水平与疾病活动度呈显著正相关。
IL-37表达升高与HLA-B27相关AAU和特发性AAU的疾病活动度相关。IL-37可抑制AAU中促炎细胞因子的产生。调控IL-37可能为这些疾病提供新的治疗靶点。
