Role of Interleukin 37 as a Novel Proangiogenic Factor in Juvenile Idiopathic Arthritis.

OBJECTIVE: The aim of this study was to investigate interleukin 37 (IL-37) levels in the serum and synovial fluid of patients with juvenile idiopathic arthritis (JIA), its expression in peripheral blood mononuclear cells, and correlation with disease activity and angiogenesis.

METHODS: Seventy JIA patients and 50 control subjects were examined. The Juvenile Arthritis Disease Activity Score in 27 joints (JADAS-27) was calculated. Immunoassays were used to measure the serum and synovial fluid levels of IL-37, vascular endothelial growth factor (VEGF), soluble VEGF receptor 1 (sVEGF-R1), and sVEGF-R2. Relative expression of IL-37 mRNA in peripheral blood mononuclear cells and the power Doppler ultrasound score of the affected joint were measured.

RESULTS: Patients with JIA were subdivided as 20 systemic-onset, 20 polyarticular, and 30 oligoarticular (10 persistent, 20 extended) cases. Serum levels of IL-37, VEGF, VEGF-R1, and VEGF-R2 and relative IL-37 mRNA expression were significantly higher in JIA patients when compared with the control subjects (P < 0.001). These concentrations were significantly higher in systemic-onset JIA compared with those in polyarticular and oligoarticular JIA, and in polyarticular JIA when compared with oligoarticular JIA (P < 0.001). Serum, synovial, and mRNA expression levels of IL-37 were positively correlated with C-reactive protein, erythrocyte sedimentation rate, Juvenile Arthritis Disease Activity Score in 27 joints, power Doppler ultrasound score (P < 0.001), and the serum and synovial VEGF and VEGF-RI and -R2 levels (P < 0.05).

CONCLUSIONS: Our results demonstrate that IL-37 levels and mRNA expression were significantly increased in JIA patients, and their levels were positively correlated with disease activity and markers of angiogenesis (VEGF and VEGF receptors), suggesting that IL-37 may be correlated with angiogenesis.