title: Interleukin-19 blockade attenuates collagen-induced arthritis in rats.
abstract: OBJECTIVE
  RA is the most common form of inflammatory arthritis. IL-19 acts as a pro-inflammatory cytokine involved in the pathogenesis of RA. We investigated whether anti-IL-19 antibody treatment would modulate the severity of the disease in a CIA rat model.
  
  
  METHODS
  We generated a CIA model by immunizing rats with bovine type II collagen. CIA rats were s.c. treated with anti-IL-19 antibody 1BB1. The effects of 1BB1 on CIA rats were determined by hind-paw thickness, severity score, bone destruction, BMD and cytokine production, which were evaluated using radiological scans, micro-CT, real-time quantitative PCR and ELISA. To analyse gene regulation by IL-19, rat synovial fibroblasts (SFs) were isolated and analysed for the expression of TNF-α, IL-1β and RANK ligand (RANKL).
  
  
  RESULTS
  In vivo, IL-19 was highly expressed in the synovial tissue and SFs isolated from CIA rats. 1BB1 significantly ameliorated the severity of arthritis by decreasing hind-paw thickness and swelling; prevented bone destruction and bone loss; inhibited the expression of TNF-α, IL-1β, IL-6 and RANKL in synovial tissue; and decreased the production of IL-6 in serum. In vitro, IL-19-induced TNF-α, IL-1β, IL-6 and RANKL expression in CIA SFs.
  
  
  CONCLUSIONS
  Specifically blocking IL-19 inhibited pro-inflammatory cytokine production and prevented bone destruction in CIA rats. These findings provide evidence that IL-19 is a novel target, and that anti-IL-19 antibody may be a potential target to ameliorate the severity of RA.
authors: Department of Biochemistry and Molecular Biology, National Cheng Kung University, Tainan, Taiwan.
authors: Yu-Hsiang
authors: YH
authors: Hsu
authors: Pei-Pei
authors: PP
authors: Hsieh
authors: Ming-Shi
authors: MS
authors: Chang
mesh_terms: D000818:Animals; D019138:Antibodies, Blocking / Q000627:therapeutic use*; D001169:Arthritis, Experimental / Q000000981:diagnostic imaging / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015519:Bone Density / Q000187:drug effects; D004797:Enzyme-Linked Immunosorbent Assay; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005786:Gene Expression Regulation; D007150:Immunohistochemistry; D016753:Interleukin-10 / Q000276:immunology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood; D007378:Interleukins; D008297:Male; D053245:RANK Ligand / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D012720:Severity of Illness Index; D013583:Synovial Membrane / Q000187:drug effects / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D055114:X-Ray Microtomography
chemical_list: D019138:Antibodies, Blocking; C498891:Il19 protein, mouse; D053583:Interleukin-1beta; D015850:Interleukin-6; D007378:Interleukins; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10