title: Interleukin 17 levels are increased in juvenile idiopathic arthritis synovial fluid and induce synovial fibroblasts to produce proinflammatory cytokines and matrix metalloproteinases.
abstract: OBJECTIVE
  Cytokines are the major mediators of joint damage in chronic arthritis. Data on synovial fluid (SF) concentration of Th17 cell-derived cytokine interleukin 17 (IL-17) in patients with juvenile idiopathic arthritis (JIA) are sparse. We measured levels of IL-17 in SF specimens from children with enthesitis-related arthritis (ERA) and polyarticular JIA (poly-JIA), and studied the ability of IL-17 to produce matrix metalloproteinases (MMP) and cytokines by fibroblast-like synoviocytes (FLS) from patients with ERA.
  
  
  METHODS
  IL-17 levels were measured in SF of patients with ERA (n = 43), poly-JIA (n = 17), rheumatoid arthritis (RA; n = 35), and osteoarthritis (OA; n = 10) by ELISA. In patients with JIA, 10 paired serum samples were also assayed. FLS were cultured from SF of patients with ERA and subsequently stimulated for 48 h by IL-17 or tumor necrosis factor-alpha. Later the production of IL-6, IL-8, MMP-1, MMP-3, and tissue inhibitor of metalloproteinase (TIMP)-1 was measured in the culture supernatants by ELISA.
  
  
  RESULTS
  Median IL-17 levels in SF were higher in patients with JIA [28 pg/ml (range 0-200)] compared to OA [0 pg/ml (range 0-84); p < 0.001] and RA (p < 0.05). The levels were comparable between poly-JIA patients and the ERA group. The median SF IL-17 levels were significantly higher compared to serum levels in children with JIA (p < 0.005). In ERA, SF IL-17 correlated with number of swollen joints (r = 0.35; p < 0.05), number of joints with limited mobility (r = 0.55; p < 0.001), and number of tender joints (r = 0.46; p < 0.01); however, no correlation was seen with erythrocyte sedimentation rate. IL-17 induced FLS to produce IL-6, IL-8, MMP-3, and MMP-1. However, there was no effect on the production of TIMP.
  
  
  CONCLUSIONS
  Increased IL-17 levels in ERA SF correlate with disease activity and this may be due to increased production of MMP and cytokines by IL-17.
authors.affiliation: Department of Immunology, Sanjay Gandhi Postgraduate Institute of Medical Sciences, Lucknow, India.
authors.forename: Shilpi
authors.initials: S
authors.lastname: Agarwal
authors.forename: Ramnath
authors.initials: R
authors.lastname: Misra
authors.forename: Amita
authors.initials: A
authors.lastname: Aggarwal
mesh_terms: D000293:Adolescent; D000328:Adult; D001171:Arthritis, Juvenile / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000276:immunology*; D016022:Case-Control Studies; D002478:Cells, Cultured; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D005347:Fibroblasts / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000032:analysis / Q000097:blood / Q000276:immunology*; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000378:metabolism; D020782:Matrix Metalloproteinases / Q000378:metabolism; D010003:Osteoarthritis / Q000276:immunology; D013582:Synovial Fluid / Q000276:immunology*
chemical_list: C508606:CXCL8 protein, human; D016207:Cytokines; C508600:IL6 protein, human; D020381:Interleukin-17; D015850:Interleukin-6; D016209:Interleukin-8; D020782:Matrix Metalloproteinases; D019278:Matrix Metalloproteinase 3; D020781:Matrix Metalloproteinase 1