Interleukin‐20 is triggered by TLR ligands and associates with disease activity in patients with rheumatoid arthritis
Background: Interleukin (IL)‐20 is a pro‐inflammatory cytokine that may be implicated in the pathogenesis of rheumatoid arthritis (RA). This study aimed to determine the association between IL‐20 and disease activity in patients with RA. Methods: The levels of serum and synovial fluid IL‐20 were measured in patients with RA and OA. The disease activity was assessed based on the Disease Activity Score of 28 joints (DAS28). The expression of IL‐20 in synovial tissue samples from patients with RA and OA were determined by immunohistochemistry. Immunofluorescence staining was used to co‐localize IL‐20 with selected cells. The secretion of IL‐20 was analysed in human peripheral blood mononuclear cells (PBMCs) of patients with RA. Results: Synovial fluid and synovial tissue IL‐20 were significantly increased in patients with RA compared with patients with OA. The expression of IL‐20 in RA synovial tissue was particularly associated with macrophages and neutrophil granulocytes, but also with synovial fibroblasts and lymphocytes. The IL‐20 levels in synovial fluid correlated with DAS28 (r = 0.434; p = 0.015) and were significantly elevated in anti‐CCP positive RA compared with anti‐CCP negative RA (122.3 ± 104.1 pg/ml and 45.9 ± 35.8 pg/ml; p = 0.008). IL‐20 production from PBMCs was induced by Poly I:C and LPS but not with pro‐inflammatory cytokines, such as TNF‐&agr; or IL‐1. Conclusion: Our data showed that IL‐20 is independently associated with RA disease activity and may be triggered by TLR ligands at local sites of inflammation. HighlightsElevated synovial fluid IL‐20 is associated with RA disease activity.IL‐20 levels are higher in anti‐CCP positive RA patients.IL‐20 production from PBMCs is induced by TNF‐independent TLR pathways.