Chen Bingni, Huang Kunzhao, Ye Liang, Li Yanqun, Zhang Jiawei, Zhang Jinshun, Fan Xinmin, Liu Xiaokai, Li Li, Sun Jinxia, Du Jing, Huang Zhong
Biological therapy institute, Shenzhen University School of Medicine, Shenzhen, 518060, Guangdong, China.
Department of Pathogen biology and immunology, Shenzhen University School of Medicine, Shenzhen, 518060, China.
J Transl Med. 2015 Jan 28;13:36. doi: 10.1186/s12967-015-0394-3.
Interleukin-37 (IL-37) has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of ankylosing spondylitis (AS) has not been investigated. Here, we examined the serum levels of IL-37 and its clinical association in AS, and explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from AS patients.
The mRNA levels of IL-37, TNF-α, IL-6, IL-17, and IL-23 in PBMCs and their serum concentrations from 46 AS patients were examined by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunoassay (ELISA), respectively. The correlations between serum IL-37 levels with disease activity, laboratory values and pro-inflammatory cytokines in AS were analyzed by Spearman correlation test. PBMCs from 46 AS patients were stimulated with recombinant IL-37 protein, expressions of TNF-α, IL-6, IL-17 and IL-23 were determined by RT-PCR and ELISA.
Compared to healthy controls (HC), AS patients and active AS patients showed higher levels of IL-37 in PBMCs and serum respectively. Strikingly, serum IL-37 levels were higher in AS patients with osteoporosis than those without. Serum levels of IL-37 were correlated with laboratory values as well as TNF-α, IL-6 and IL-17, but not IL-23 in patients with AS. The productions of pro-inflammatory cytokines such as TNF-α, IL-6, IL-17, IL-23 in PBMCs from AS patients were obviously attenuated after recombinant IL-37 stimulation, but not in the HC.
The higher levels of IL-37 were found in AS patients, which were correlated with disease activity and AS related pro-inflammatory cytokines. More importantly, IL-37 inhibits the expressions of the pro-inflammatory cytokines from PBMCs in AS patients, indicating the potential anti-inflammatory role of IL-37 in AS.
白细胞介素-37（IL-37）在多种炎症性疾病中发挥免疫抑制作用，但它是否参与强直性脊柱炎（AS）发病机制的调控尚未见研究报道。在此，我们检测了AS患者血清中IL-37水平及其临床相关性，并探讨了IL-37对AS患者外周血单个核细胞（PBMCs）的抗炎作用。
分别采用实时聚合酶链反应（RT-PCR）和酶联免疫吸附测定（ELISA）检测46例AS患者PBMCs中IL-37、TNF-α、IL-6、IL-17和IL-23的mRNA水平及其血清浓度。采用Spearman相关性检验分析AS患者血清IL-37水平与疾病活动度、实验室指标及促炎细胞因子之间的相关性。用重组IL-37蛋白刺激46例AS患者的PBMCs，通过RT-PCR和ELISA检测TNF-α、IL-6、IL-17和IL-23的表达。
与健康对照（HC）相比，AS患者及活动期AS患者PBMCs和血清中IL-37水平分别更高。令人惊讶的是，合并骨质疏松的AS患者血清IL-37水平高于未合并骨质疏松的患者。AS患者血清IL-37水平与实验室指标以及TNF-α、IL-6和IL-17相关，但与IL-23无关。重组IL-37刺激后，AS患者PBMCs中TNF-α、IL-6、IL-17、IL-23等促炎细胞因子的产生明显减弱，但HC组无此现象。
AS患者中发现较高水平的IL-37，其与疾病活动度及AS相关促炎细胞因子相关。更重要的是，IL-37抑制AS患者PBMCs中促炎细胞因子的表达，提示IL-37在AS中具有潜在的抗炎作用。
