OBJECTIVE: To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity. METHODS: Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokine levels (IL-1beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test. RESULTS: All the analyzed cytokine levels (IL-1, IL-1Ra, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes. CONCLUSION: Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis.
OBJECTIVE: To verify the importance of interleukin 18 (IL-18) in the pathogenesis of juvenile idiopathic arthritis (JIA). We measured IL-18 levels in synovial fluid (SF) and serum, and determined their correlation with measures of disease activity and severity. METHODS: Fifty patients with JIA (13 systemic, 13 polyarticular, 24 oligoarticular) and 25 matched controls were analyzed. Cytokine levels (IL-1beta, IL-1Ra, IL-6, and IL-18) were quantified in serum and SF by ELISA, and disease activity measures were evaluated immediately after knee articular puncture. Radiological assessment was made according to the Steinbrocker method. Statistical analysis was performed by Spearman's rank-order correlation and Mann-Whitney rank test. RESULTS: All the analyzed cytokine levels (IL-1, IL-1Ra, IL-6, and IL-18) were higher in patients' sera than in controls. Remarkably, in patients with JIA, IL-18 SF levels did not differ from those of serum; they were positively correlated. The levels of IL-18 (SF and serum) were positively correlated with measures of disease activity: C-reactive protein, number of active joints, and radiological score, as well as with levels of IL-1, IL-1Ra, and IL-6. Moreover, IL-18 and IL-6 levels in SF and serum were much higher in patients with systemic disease compared to the other types of disease onset. In contrast, IL-1 and IL-1Ra were not different among JIA subtypes. CONCLUSION: Our results strongly suggest the participation of IL-18 in the pathophysiology of JIA. The positive correlation of this cytokine with several measures of articular inflammation and disease severity suggests that IL-18 could be a better target for the treatment of arthritis.
Authors: Joong-Ho Won; Ofir Goldberger; Shai S Shen-Orr; Mark M Davis; Richard A Olshen Journal: Proc Natl Acad Sci U S A Date: 2012-02-09 Impact factor: 11.205