白细胞介素-38，一种潜在的狼疮治疗药物，可抑制狼疮进展。

IL-38, a potential therapeutic agent for lupus, inhibits lupus progression.

机构信息

Department of Evidence-Based Medicine, Southwest Medical University, 1 Xianglin Road, Luzhou, 646000, Sichuan, China.

Department of Rheumatology and Immunology, Minda Hospital of Hubei Minzu University, 2 Wufengshan Road, Enshi, 445000, Hubei, China.

出版信息

Inflamm Res. 2022 Aug;71(7-8):963-975. doi: 10.1007/s00011-022-01581-3. Epub 2022 Jul 1.

DOI:10.1007/s00011-022-01581-3

PMID:35776155

Abstract

BACKGROUND

Previous studies reported that IL-38 was abnormally expressed in patients with systemic lupus erythematosus (SLE). However, the involvement of IL-38 in the pathophysiology of SLE remains unknown.

METHODS

The therapeutic potential of IL-38 was tested in pristane-treated wild-type (WT) and IL-38 mice. Thus, SLE was induced via pristane in WT and IL-38 mice. Afterwards, the liver, spleen, and kidney of each mouse were obtained. The flow cytometric analysis of the immune cells, serologic expression of inflammatory cytokines and autoantibodies, renal histopathology, and inflammatory signaling were evaluated.

RESULTS

WT mice with pristane-induced lupus exhibited hepatomegaly, splenomegaly, severe kidney damages, increased lymphoproliferation, enhanced lymphoproliferation, and upregulated inflammatory cytokines, such as IL-6, IL-13, IL-17A, MIP-3α, IL-12p70, and IFNγ, and elevated levels of autoantibodies, such as ANA IgG, anti-dsDNA IgG, and total IgG. IL-38 mice whose lupus progressed, had elevated cells of CD14, CD19, CD3, and Th1, upregulated inflammatory cytokines and autoantibodies, and severe pathological changes in kidney. Administration of recombinant murine IL-38 to pristane-treated IL-38 mice improved their renal histopathology, which depended on ERK1/2, JNK1/2, p38, NF-κB p65, and STAT5 signaling pathways.

CONCLUSION

IL-38 regulates SLE pathogenesis. Furthermore, targeting IL-38 is critical in the treatment of SLE.

摘要

背景

先前的研究表明白细胞介素-38（IL-38）在系统性红斑狼疮（SLE）患者中异常表达。然而，IL-38 参与 SLE 的病理生理学过程尚不清楚。

方法

在经 pristane 处理的野生型（WT）和 IL-38 小鼠中测试了 IL-38 的治疗潜力。因此，在 WT 和 IL-38 小鼠中通过 pristane 诱导 SLE。之后，获得每只小鼠的肝、脾和肾。评估免疫细胞的流式细胞分析、炎症细胞因子和自身抗体的血清学表达、肾脏组织病理学和炎症信号转导。

结果

经 pristane 诱导狼疮的 WT 小鼠表现出肝肿大、脾肿大、严重的肾脏损伤、淋巴增殖增强、炎症细胞因子（如 IL-6、IL-13、IL-17A、MIP-3α、IL-12p70 和 IFNγ）上调以及自身抗体（如 ANA IgG、抗 dsDNA IgG 和总 IgG）水平升高。狼疮进展的 IL-38 小鼠，其 CD14、CD19、CD3 和 Th1 细胞升高，炎症细胞因子和自身抗体上调，肾脏病理变化严重。向经 pristane 处理的 IL-38 小鼠给予重组鼠 IL-38 可改善其肾脏组织病理学，这取决于 ERK1/2、JNK1/2、p38、NF-κB p65 和 STAT5 信号通路。