Clinical immunology
Interleukin-6 and tumor necrosis factor alpha levels in the serum and synovial fluid in relation to bone mineral density and turnover in children with juvenile idiopathic arthritis

Aim of the study:
To evaluate the relationships between levels of proinflammatory cytokines (TNF-α and IL-6) and bone metabolism in juvenile idiopathic arthritis (JIA) children.

Methods:
Twenty children with active JIA were included, 12 with polyarticular type of JIA and 8 with oligoarticular onset. The control group consisted of 15 healthy children. TNF-α and IL-6 were measured in the serum and synovial fluid using ELISA Quantikine kits (R & D Systems, USA). The levels of osteocalcin (N-MID Osteocalcin) and C-terminal type I alpha-collagen chain telopeptide (CTx) were determined in the Elecsys® 2010 system. Bone mineral density (BMD) was assessed by DXA method in the total bone (Total BMD, g/cm2) and in the L2-L4 vertebrae (SpineBMD, g/cm2) as Z-score.

Results:
In children with JIA, the mean serum IL-6 level was elevated as compared with the control group (34.5 pg/ml ± 31.9 and 1.4 ± 1.6 pg/ml, respectively, p<0.01). The level of TNF-α in JIA children was higher (9.3 pg/ml ± 3.9) in comparison with the control group (4.7 pg/ml ± 0.5), but the difference was not statistically significant. In both JIA forms, the level of IL-6 in synovial fluid was high (442.8 pg/ml ± 162.2). The mean levels of N-MID Osteocalcin and CTx were increased as compared with the control group (96.3 ng/ml ± 54.0 and 70.2 ng/ml ± 48.3; 1.7 µg/dl ± 0.5 and 1.2 µg/dl ± 0.4, respectively). A significant positive correlation was observed between ESR and serum IL-6 level (p<0.04) and the degree of articular damage (p<0.001). There was a trend toward negative correlation between serum IL-6 and TNF-α levels and bone mineral density (p=0.05 for both).

Conclusions:
Elevated levels of IL-6, TNF-α, N-MID osteocalcin, CTx and significant correlations between inflammatory parametrs, articular destruction and bone mass loss were observed in patients with JIA.