Abstract

BackgroundInterleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines.MethodsThe mRNA levels of IL-37 in PBMCs and plasma IL-37 concentrations in 46 sJIA patients and 30 age- and sex-matched healthy controls were measured by real-time polymerase chain reaction (RT-PCR) and enzyme-linked immunosorbent assay (ELISA), respectively. The correlations between plasma IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines in sJIA were analyzed by Spearman correlation test. PBMCs from the sJIA patients were stimulated with recombinant human IL-37 (rhIL-37) protein, expressions of IL-1β, IL-6, TNF-α and IL-17 were detected by RT-PCR and ELISA.ResultsPlasma levels of IL-37 and relative IL-37 mRNA expression were significantly elevated in sJIA patients, especially in active sJIA patients, when compared with the healthy controls (P < 0.001). Furthermore, patients with active disease showed higher IL-37 mRNAs and plasma protein levels than those with inactive disease as well as healthy controls. Plasma IL-37 levels were correlated with disease activity and inflammatory cytokines (IL-6, TNF-α, IL-17 and GM-CSF) in sJIA patients. The productions of inflammatory cytokines such as IL-6, TNF-α, IL-17 in PBMCs from sJIA patients were obviously decreased after recombinant IL-37 stimulation, whereas the production of IL-1β was not changed.ConclusionsOur results demonstrate that levels of IL-37 were higher in sJIA patients, which were correlated with disease activity and sJIA related inflammatory cytokines. In addition, rhIL-37 down-regulates the expressions of inflammatory cytokines form PBMCs in sJIA patients, suggesting that IL-37 may have the potential role as a natural inhibitor for the pathogenesis and therapy of sJIA.

Highlights

  • Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response

  • IL-37 mRNA expression in peripheral blood mononuclear cells (PBMCs) was measured by real-time polymerase chain reaction (RT-PCR) and the plasma protein levels were detected by enzyme-linked immunosorbent assay (ELISA)

  • The results showed that IL-37 mRNA and plasma protein levels were significantly higher in systemic juvenile idiopathic arthritis (sJIA) patients compared with healthy controls (HCs) (Fig. 1), indicating that IL-37 probably participated in the pathogenesis of sJIA

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Summary

Introduction

Interleukin (IL)-37 has emerged as a novel anti-inflammatory cytokine that play an immunosuppressive role in regulating inflammatory response. This study aimed to measure IL-37 levels in the plasma and peripheral blood mononuclear cells (PBMCs) of patients with systemic juvenile idiopathic arthritis (sJIA), and to establish the correlation between IL-37 levels and disease activity, laboratory parameters and inflammatory cytokines. The pathogenesis of sJIA remains unclear, more and more research indicated that inflammatory cytokines were involved in the regulation of systemic inflammation, local joints damage and bone erosion [2]. It seems that the balance between pro- and anti-inflammatory cytokines may play a vital role in the pathogenesis and progression of sJIA. IL-37, formerly named IL-1F7, downregulated the expression of pro-inflammatory cytokines in various inflammatory diseases [11], such as ankylosing spondylitis (AS), systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and adult-onset Still’s disease (AOSD) [12,13,14,15,16], relieving the inflammatory responses in sJIA

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