title: Th-17 associated cytokines in patients with reactive arthritis/undifferentiated spondyloarthropathy.
abstract: We and others have previously shown that IL-17 is elevated in the synovial fluid of patients with reactive arthritis (ReA)/undifferentiated spondyloarthropathy (uSpA) having acute synovitis. Major source for IL-17 is Th17 cells, which differentiate from Th0 cells under the influence of TGF-β and IL-6, IL1-β and are maintained by IL-21 and 23. There is a paucity of data on these cytokines in ReA/uSpA. Thus, we measured the levels of Th-17 differentiating and maintaining cytokines in synovial fluid of patients with ReA and uSpA. Fifty patients with ReA/uSpA (ReA 24, uSpA 26), 19 patients with rheumatoid arthritis (RA) and 11 patients with osteoarthritis (OA) were included in the study. Synovial fluid (SF) were collected from knee joint and stored at -80°C until analysis. Cytokines were assayed using ELISA in SF specimens. The median IL-17A levels were significantly elevated in ReA (48.3 pg/ml) and uSpA (32.5 pg/ml) as compared to non-inflammatory OA controls (<7.8 pg/ml; p < 0.0001), while comparable to RA (57.9 pg/ml). Further, IL-6 median values were higher in ReA (25.2 ng/ml) and uSpA (13.6 ng/ml) as compared to OA (0.76 ng/ml; p < 0.0001), and comparable to RA (15.8 ng/ml). The median levels of IL-1β, IL-21 levels were elevated in ReA, uSpA and RA as compared to OA but were not statistically significant. TGF-β levels in ReA and uSpA were similar to OA but lower than in RA (4340 pg/ml; p < 0.05). IL-23 was not detectable in any synovial fluid sample. However, levels of these cytokines did not correlate with disease activity parameters. Significant positive correlation was observed between IL-17 and IL-1β (r = 0.38, p < 0.005), IL-17 and IL-6 (r = 0.659, p < 0.0001), and IL-1β and IL-6 (r = 0.391, p < 0.0001) in ReA and uSpA group. Inflammatory synovitis in ReA/uSpA is mediated by pro-inflammatory cytokines like IL-17, IL-6, IL-1β, and IL-21. However, IL-23 was not detectable in SF. Good correlation between IL-17, IL-6, and IL 1β suggest that either they are co-regulated or they regulate each other.
authors.affiliation: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Amit Kumar
authors.initials: AK
authors.lastname: Singh
authors.forename: Ramnath
authors.initials: R
authors.lastname: Misra
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
mesh_terms: D000328:Adult; D016918:Arthritis, Reactive / Q000378:metabolism*; D001172:Arthritis, Rheumatoid / Q000378:metabolism; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D020381:Interleukin-17 / Q000378:metabolism*; D053583:Interleukin-1beta / Q000378:metabolism*; D053759:Interleukin-23 / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D007378:Interleukins / Q000378:metabolism; D008297:Male; D010003:Osteoarthritis / Q000378:metabolism; D000091402:Prohibitins; D012189:Retrospective Studies; D025242:Spondylarthropathies / Q000378:metabolism*; D013582:Synovial Fluid / Q000378:metabolism*; D013585:Synovitis / Q000378:metabolism; D058504:Th17 Cells / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D000098546:Interleukin-21
chemical_list: D020381:Interleukin-17; D053583:Interleukin-1beta; D053759:Interleukin-23; D015850:Interleukin-6; D007378:Interleukins; C000717331:PHB2 protein, human; D000091402:Prohibitins; D016212:Transforming Growth Factor beta; D000098546:Interleukin-21