engleski

Interleukin-18 as a mediator of systemic juvenile idiopathic arthritis (JIA)

Juvenile idiopathic arthritis (JIA) comprises a heterogeneous group of diseases with unknown aetiology. The immunoregulatory abnormalities, including abnormal cytokine production, are thought to be important in the pathogenesis of JIA. However, the key mediators have not yet been elucidated. Aim was to determine the serum and synovial fluid levels of IL-18 in patients with JIA, and to explore the association of those levels with the status and activity of disease. The study was performed at the Department of Paediatric Rheumatology and the Laboratory of Immunology of the Zagreb University Hospital Centre, Zagreb, Croatia. Fifty – one child with JIA (mean age (± ; SD) 11.2 ± ; 2.5 yr ; 33 girls, 18 boys) and 8 healthy children (mean age 6.8 ± ; 4.7 yr) were enrolled. Thirty-one patients had oligoarticular JIA, 14 polyarticular JIA and 6 systemic JIA. Peripheral blood was obtained from the patients in active and inactive period. Synovial fluid samples were collected from 15 patients with oligoarticular JIA. IL-18 was measured using a commercially ELISA kit (MBL, Japan). The study was approved by the Ethics Committee of the Zagreb University School of Medicine. The groups were compared by ANOVA, followed by Student-Newman-Keuls post hoc test, while the differences within a group (i.e. active vs. inactive disease) were analyzed by paired Student's t-test. The associations between IL-18 levels and laboratory tests were analyzed using Pearson’ s correlation coefficient. The α -level was set at 0.05. Serum levels of IL-18 in patients with systemic JIA were significantly higher than in patients with other forms of disease, both in active and inactive phase (P < 0.05 ; ANOVA), while the IL-18 levels in children with oligoarticular and polyarticular JIA were comparable to the healthy children (Table 1). The concentrations of IL-18 in patients with systemic JIA decreased significantly during the inactive phase of disease (P < 0.05 ; paired Student's t-test) but remained several-fold higher in comparison to the other groups (P < 0.05 ; ANOVA). Synovial fluid levels of IL-18 (247 ± ; 205 pg/mL) did not differ significantly from the serum levels in oligoarticular JIA (Table 1). In addition, the serum levels of IL-18 were proportional to the erythrocyte sedimentation rate (Pearson's r = 0.55, P < 0.05) and levels of C-reactive protein (Pearson's r = 0.49, P < 0.05), while being inversely proportional to the concentrations of haemoglobin (Pearson's r = -0.47, P < 0.05) and serum concentrations of IgG (Pearson's r = -0.27, P < 0.05). We found no association between the IL-18 and levels of γ -globulins in plasma (Pearson's r = -0.11, P = 0.46). These results indicate that the IL-18 is involved in the pathogenesis of the systemic form of JIA. The levels of IL-18 correlated rather well with the other indicators of systemic inflammation and were relatively high during the clinical remission of the disease. Moreover, it seems that the joints were not the main site of IL-18 production. Taken together our data imply that systemic production of IL-18 might be important for the pathogenesis of systemic JIA. Therefore, patients with severe systemic JIA, uncontrolled by conventional therapy, might benefit from the biological agents targeting IL-18.

juvenile idiopathic artritis; interleukin-18

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