Long-Term Follow-Up of Cytokines and Soluble Cytokine Receptors in Peripheral Blood of Patients with Juvenile Rheumatoid Arthritis

Plasma levels of interleukin-1 beta (IL-1 beta), IL-2, soluble IL-2 receptor (sIL-2R), IL-6, IL-8, tumor necrosis factor- alpha (TNF- alpha), and the p60 soluble TNF receptor (sTNFR) were repeatedly determined by enzyme-linked immunosorbent assays (ELISA) in 35 patients with different subtypes of juvenile rheumatoid arthritis (JRA) during an observation period of up to 36 months. The data were related to conventional inflammatory parameters and disease activity. Patients with systemic disease showed the most pronounced elevations of plasma cytokines, followed by polyarticular and pauciarticular JRA. Soluble receptors sIL-2R and sTNFR were consistently elevated in patients of all JRA subtypes and indicated disease activity even in patients with normal C-reactive protein (CRP). In contrast, the determination of IL-1 beta, IL-2, IL-8, and TNF- alpha revealed strikingly different individual profiles in patients of the same clinical subtype of JRA and irrespective of disease activity. It is concluded that the determination of sIL-2R and sTNFR may be relevant for monitoring JRA, as they indicate disease activity also in cases with unaltered conventional inflammatory parameters. The different individual cytokine profiles of patients within identical subtypes of disease suggest JRA to be even more heterogeneous than hitherto assumed. The data should be considered in attempts to develop anticytokine strategies in the therapy of JRA.