Contribution of interleukin 17 to synovium matrix destruction in rheumatoid arthritis

Cytokine. 2000 Jul;12(7):1092-9. doi: 10.1006/cyto.2000.0681.


Interleukin (IL-)17 is a T cell-derived pro-inflammatory cytokine produced by RA synovium. We studied the role of IL-17 in the synovium cytokine network to determine whether it can influence the inflammatory and destructive pattern characteristic of RA. Herein, we investigated whether the production and action of MMP-1 and its inhibitor TIMP-1 could be modulated by IL-17 in the presence of pro-inflammatory cytokine (IL-1) and anti-inflammatory cytokines (IL-4, IL-13, IL-10). The effect of the blockade of endogenous IL-17 on the secretion of MMP-1 and TIMP-1 by RA synovium and matrix destruction was also studied. IL-17 increased the spontaneous production of MMP-1 by synoviocytes five-fold. IL-1 was more potent since it increased MMP-1 production nine-fold. Addition of IL-4, IL-13 and IL-10 to synoviocyte cultures reduced the spontaneous production of MMP-1 and induced TIMP-1 production by synoviocytes stimulated with IL-17 or/and IL-1beta. In the presence of anti-IL-17 blocking mAb, MMP-1 production and collagenase activity by RA synovium was reduced by 50% and associated with a 50% reduction in type I collagen C-telopeptide fragments (CTX) released in the supernatants, demonstrating the direct contribution of IL-17 in destruction. IL-17 and its producing T cells appear to contribute to the inflammatory process involved in the rheumatoid lesion.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Arthritis, Rheumatoid / immunology*
  • Arthritis, Rheumatoid / pathology
  • Cells, Cultured
  • Collagenases / metabolism
  • Humans
  • Interleukin-10 / pharmacology
  • Interleukin-13 / pharmacology
  • Interleukin-17 / immunology*
  • Interleukin-4 / pharmacology
  • Matrix Metalloproteinase 1 / biosynthesis
  • Synovial Membrane / cytology
  • Synovial Membrane / immunology
  • Th2 Cells / immunology
  • Tissue Inhibitor of Metalloproteinase-1 / biosynthesis


  • Interleukin-13
  • Interleukin-17
  • Tissue Inhibitor of Metalloproteinase-1
  • Interleukin-10
  • Interleukin-4
  • Collagenases
  • Matrix Metalloproteinase 1