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OBJECTIVE: Data on synovial fluid (SF) cytokine concentrations in patients with reactive arthritis (ReA) or undifferentiated spondyloarthropathy (uSpA) are limited and contradictory. We measured levels of several proinflammatory and immunoregulatory cytokines in SF and sera from patients with ReA/uSpA. METHODS: Interleukin 17 (IL-17), IL-6, interferon-g (IFN-g), and IL-12p40, and immunoregulatory cytokines IL-10 and transforming growth factor-beta (TGF-beta) were assayed using ELISA in SF specimens from 51 patients with ReA/uSpA (ReA 21, uSpA 30), 40 patients with rheumatoid arthritis (RA), and 11 patients with osteoarthritis (OA). IL-17, IL-6, IFN-g, and IL-10 levels were also measured in paired sera samples from patients with ReA/uSpA. RESULTS: SF concentrations of IL-17, IL-6, TGF-beta, and IFN-g were significantly higher in patients with ReA/uSpA as compared to RA patients (for IL-17 median 46 pg/ml, range < 7.8-220 vs median < 7.8 pg/ml, range < 7.8-136, p < 0.05; for TGF-beta median 4.2 ng/ml, range 1.32-12 vs median 3.01 ng/ml, range 0.6-9.6, p < 0.01; for IL-6 median 58 ng/ml, range 2-540 vs median 34.5 ng/ml, range < 0.009-220, p < 0.05; for IFN-g median 290 pg/ml, range < 9.4-1600 vs median 100 pg/ml, range < 9.4-490, p < 0.05). SF levels of IL-10 were comparable but the ratio of IFN-g/IL-10 was significantly higher in ReA/uSpA patients than RA patients (median 3.18, range 0.06-200 for ReA/uSpA vs median 1.0, range 0.03-26.9 for RA; p < 0.05). IL-17, IL-6, IL-10, and IFN-g SF levels were significantly higher than paired serum levels in ReA/uSpA patients (p < 0.01 for IL-17, p < 0.0001 for IL-6, p < 0.0001 for IL-10, and p < 0.001 for IFN-g). CONCLUSION: Increased IL-17, IL-6, TGF-beta, and IFN-g concentrations in ReA/uSpA than in RA suggest that Th1 and Th17 cells could be the major agents in inflammation in ReA/uSpA.