Background/Purpose

 Innate proinflammatory cytokines interleukin (IL)-6 and IL-18 are critical for perpetuating the inflammatory processes in systemic juvenile idiopathic arthritis (s-JIA) and macrophage activation syndrome (MAS). To assess the role of IL-6 and IL-18 in the pathogenesis of s-JIA and MAS, and to investigate the clinical significance of serum cytokine profile with IL-6 and IL-18 in s-JIA and MAS, we analyzed the serum IL-6 and IL-18 in patients with s-JIA and compared them with the clinical features of s-JIA.

Methods

 71 patients with s-JIA including 23 patients with MAS were analyzed. Levels of IL-6 and IL-18 were quantified in serum by enzyme-linked immunosorbent assay. Results were compared with clinical features of s-JIA.

Results 

 Two distinct s-JIA patient subsets based on their serum IL-6 and IL-18 levels were identified: an IL-18 dominant (IL-18/IL-6>1000) and an IL-6 dominant (IL-18/IL-6<1000). The IL-6 dominant subset had a significantly greater number of joints with active disease and higher serum levels of matrix metalloproteinase-3, whereas the IL-18-dominant subset was more likely to develop MAS. The cut off value of serum IL-18 to predict the development of MAS was 52500pg/ml with 91.3% of sensitivity and 81.3% of specificity. The patients with IL-18 dominant pattern were likely to have monophasic or polycyclic disease course, whereas the patients with IL-6 dominant pattern were likely to have persistent disease course. Serum IL-18 levels in patients achieved remission decreased to the levels <1,000 pg/mL in inactive phase and normalized in remission phase. In contrast, serum IL-18 levels in patients experienced relapse during withdrawal of steroid within 12 months after disease onset demonstrated a sustained elevation of serum IL-18 levels (>1,000 pg/mL) during the inactive phase.

Conclusion

 Two subsets of patients with s-JIA, one which is prone for arthritis and another with prone for MAS, can be identified on the basis of their serum IL-6 and IL-18 levels. These two subsets appear to be characterized by certain distinct clinical features. Monitoring the cytokine profile with IL-18 and IL-6 might be useful to predict disease course. Furthermore, serum IL-18 levels reflect the biological activities of the immune system in s-JIA and may predict the development of MAS and the prognosis of s-JIA.

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ACR Meeting Abstracts - https://acrabstracts.org/abstract/clinical-significance-of-cytokine-profile-with-interleukin-18-and-6-in-systemic-juvenile-idiopathic-arthritis/