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IL-37 抑制系统性红斑狼疮患者外周血单个核细胞中炎症细胞因子的产生:与疾病活动的相关性。

IL-37 inhibits the production of inflammatory cytokines in peripheral blood mononuclear cells of patients with systemic lupus erythematosus: its correlation with disease activity.

机构信息

Biological therapy institute, Shenzhen University School of Medicine, 518060 Shenzhen, China.

出版信息

J Transl Med. 2014 Mar 16;12:69. doi: 10.1186/1479-5876-12-69.

DOI:10.1186/1479-5876-12-69
PMID:24629023
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC4003851/
Abstract

BACKGROUND

Interleukin-37 (IL-37), a new member of IL-1 family cytokine, is recently identified as a natural inhibitor of innate immunity. This study aimed to measure the peripheral blood mononuclear cells (PBMCs) and serum levels of IL-37 in patients with systemic lupus erythematosus (SLE) and to investigate its role in SLE, including its correlation with disease activity, organ disorder and the regulation of inflammatory cytokines.

METHODS

The expressions of IL-37 mRNAs in PBMCs and serum IL-37 levels in 66 SLE patients were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA). SLE patients PBMCs were stimulated with recombinant IL-37, levels of cytokines TNF-α, IL-1β, IL-6 and IL-10 were detected by RT-PCR and ELISA.

RESULTS

IL-37 mRNAs and serum protein levels were higher in patients with SLE compared with healthy controls. Patients with active disease showed higher IL-37 mRNAs and serum protein levels compared with those with inactive disease as well as healthy controls. Serum IL-37 levels correlated with SLEDAI and inversely with C3 and C4. Serum IL-37 levels were higher in SLE patients with renal involvement compared with those without renal disease. In vitro, IL-37 inhibited the production of TNF-α, IL-1β and IL-6 in PBMCs of patients with SLE, whereas the production of IL-10 was unaffected.

CONCLUSIONS

IL-37 associated with SLE disease activity, especially related with SLE renal disease activity. IL-37 is an important cytokine in the control of SLE pathogenesis by suppressing the production of inflammatory cytokines. Thus, IL-37 may provide a novel research target for the pathogenesis and therapy of SLE.

摘要

背景

白细胞介素-37(IL-37),一种新的白细胞介素-1 家族细胞因子,最近被鉴定为先天免疫的天然抑制剂。本研究旨在测量系统性红斑狼疮(SLE)患者外周血单个核细胞(PBMC)和血清中 IL-37 的水平,并探讨其在 SLE 中的作用,包括与疾病活动、器官障碍和炎症细胞因子调节的相关性。

方法

通过实时聚合酶链反应(RT-PCR)和酶联免疫吸附试验(ELISA)测量 66 例 SLE 患者 PBMC 中 IL-37 mRNA 的表达和血清 IL-37 水平。用重组 IL-37 刺激 SLE 患者 PBMC,通过 RT-PCR 和 ELISA 检测细胞因子 TNF-α、IL-1β、IL-6 和 IL-10 的水平。

结果

与健康对照组相比,SLE 患者的 IL-37 mRNA 和血清蛋白水平更高。与无活动疾病患者和健康对照组相比,活动期疾病患者的 IL-37 mRNA 和血清蛋白水平更高。血清 IL-37 水平与 SLEDAI 相关,与 C3 和 C4 呈负相关。与无肾脏疾病的 SLE 患者相比,有肾脏受累的 SLE 患者的血清 IL-37 水平更高。在体外,IL-37 抑制 SLE 患者 PBMC 中 TNF-α、IL-1β 和 IL-6 的产生,而对 IL-10 的产生没有影响。

结论

IL-37 与 SLE 疾病活动相关,尤其是与 SLE 肾脏疾病活动相关。IL-37 是通过抑制炎症细胞因子产生来控制 SLE 发病机制的重要细胞因子。因此,IL-37 可能为 SLE 的发病机制和治疗提供新的研究靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/52cd4950d118/1479-5876-12-69-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/ff09d500f709/1479-5876-12-69-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/394bc8098b29/1479-5876-12-69-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/cce4fd092ab6/1479-5876-12-69-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/b5077de01223/1479-5876-12-69-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/52cd4950d118/1479-5876-12-69-5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/ff09d500f709/1479-5876-12-69-1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/394bc8098b29/1479-5876-12-69-2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/cce4fd092ab6/1479-5876-12-69-3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/b5077de01223/1479-5876-12-69-4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ab9f/4003851/52cd4950d118/1479-5876-12-69-5.jpg

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