Interleukin-37 is increased in adult-onset Still's disease and associated with disease activity.
BACKGROUND
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.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
['Chi|Huihui|H|', 'Liu|Dongzhou|D|', 'Sun|Yue|Y|', 'Hu|Qiongyi|Q|', 'Liu|Honglei|H|', 'Cheng|Xiaobing|X|', 'Ye|Junna|J|', 'Shi|Hui|H|', 'Yin|Yufeng|Y|', 'Liu|Mengru|M|', 'Wu|Xinyao|X|', 'Zhou|Zhuochao|Z|', 'Teng|Jialin|J|', 'Yang|Chengde|C|', 'Su|Yutong|Y|']
D000328:Adult D015415:Biomarkers D002478:Cells, Cultured D018450:Disease Progression D005260:Female D006801:Humans D007375:Interleukin-1 D007963:Leukocytes, Mononuclear D008297:Male D008875:Middle Aged D016706:Still's Disease, Adult-Onset D055815:Young Adult
IL-37 Peripheral blood mononuclear cells Cytokines Adult-onset Still’s disease