Interleukin-37 is increased in adult-onset Still’s disease and associated with disease activity

• Published in: Arthritis research & therapy Vol. 20; no. 1; pp. 54 - 12
• Main Authors: Chi, Huihui, Liu, Dongzhou, Sun, Yue, Hu, Qiongyi, Liu, Honglei, Cheng, Xiaobing, Ye, Junna, Shi, Hui, Yin, Yufeng, Liu, Mengru, Wu, Xinyao, Zhou, Zhuochao, Teng, Jialin, Yang, Chengde, Su, Yutong
• Format: Journal Article
• Language: English
• Published: England BioMed Central Ltd 22.03.2018; BioMed Central; BMC
• Subjects: Adult; Adult-onset Still’s disease; Biomarkers - blood; Cells, Cultured; Cytokines; Disease Progression; Female; Humans; IL-37; Interleukin-1 - blood; Interleukins; Leukocytes, Mononuclear - metabolism; Male; Middle Aged; Peripheral blood mononuclear cells; Physiological aspects; Still's Disease, Adult-Onset - blood; Still's Disease, Adult-Onset - diagnosis; Young Adult; Peripheral blood mononuclear cells; IL-37; Adult-onset Still’s disease; Cytokines
• ISSN: 1478-6362; 1478-6354; 1478-6362
• DOI: 10.1186/s13075-018-1555-6

Interleukin (IL)-37 has been known to play an immunosuppressive role in various inflammatory disorders, but whether it participates in the regulation of pathogenesis of adult-onset Still's disease (AOSD) has not been investigated. In this study, we examined serum IL-37 levels and their clinical association with AOSD, and we explored the anti-inflammatory effects of IL-37 on peripheral blood mononuclear cells (PBMCs) from patients with AOSD. Blood samples were collected from 62 patients with AOSD and 50 healthy control subjects (HC). The serum IL-37 levels were determined using an enzyme-linked immunosorbent assay (ELISA). The correlations of serum IL-37 levels with disease activity, laboratory values, and inflammatory cytokines in AOSD were analyzed by Spearman's correlation test. The correlations between serum IL-37 levels and clinical manifestations were analyzed by Mann-Whitney U test. PBMCs from ten patients with AOSD were stimulated with recombinant human IL-37 protein, and expression levels of tumor necrosis factor (TNF)-α, IL-6, IL-10, IL-1β, and IL-18 were determined by qRT-PCR and ELISA. A significantly higher IL-37 protein level was observed in patients with AOSD than in HC. Serum IL-37 levels correlated with systemic score, laboratory values, IL-1β, IL-18, and IL-10 in patients with AOSD. The expression levels of IL-37 were closely related to the patients with AOSD who also had fever, skin rash, lymphadenopathy, splenomegaly, myalgia, and arthralgia. Moreover, the production of proinflammatory cytokines such as IL-6, IL-1β, TNF-α, and IL-18 in PBMCs from patients with AOSD was obviously attenuated after recombinant human IL-37 stimulation. Increased expression of IL-37 and its positive correlation with disease activity suggest its involvement in AOSD pathogenesis. More importantly, IL-37 inhibits the expression of proinflammatory cytokines in PBMCs from patients with AOSD, indicating the potential anti-inflammatory role of IL-37 in AOSD. Thus, IL-37 may be a novel disease activity biomarker and research target in AOSD.