Blocking of interleukin-17 during reactivation of experimental arthritis prevents joint inflammation and bone erosion by decreasing RANKL and interleukin-1

Am J Pathol. 2005 Jul;167(1):141-9. doi: 10.1016/S0002-9440(10)62961-6.


Rheumatoid arthritis is characterized by an intermittent course of disease with alternate periods of remission and relapse. T cells, and in particular the T-cell cytokine interleukin-17 (IL-17), are expected to be involved in arthritic flares. Here, we report that neutralizing endogenous IL-17 during reactivation of antigen-induced arthritis prevents joint inflammation and bone erosion. Synovial IL-17 mRNA expression was clearly up-regulated during primary arthritis and was further enhanced after antigen rechallenge. Neutralization of IL-17 significantly prevented joint swelling at day 1 of flare and significantly suppressed joint inflammation and cartilage proteoglycan depletion at day 4, as assessed by histology. Blocking IL-17 also clearly reduced bone erosions. Cathepsin K, a marker of osteoclast-like activity, and synovial RANKL mRNA expression were both suppressed. The degree of bone erosions strongly correlated with the severity of joint inflammation, suggesting that anti-IL-17 treatment reduced bone erosion by suppressing joint inflammation. Interestingly, blocking IL-17 suppressed synovial expression of both IL-1beta and tumor necrosis factor-alpha, whereas blocking IL-1 did not affect tumor necrosis factor-alpha levels. These data indicate that IL-17 is an important upstream mediator in joint pathology during flare-up of experimental arthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / immunology*
  • Arthritis, Experimental / pathology
  • Arthritis, Rheumatoid / immunology
  • Arthritis, Rheumatoid / pathology
  • Bone and Bones / immunology
  • Bone and Bones / pathology
  • Carrier Proteins / immunology
  • Carrier Proteins / metabolism*
  • Cathepsin K
  • Cathepsins / metabolism
  • Inflammation / metabolism
  • Inflammation / prevention & control*
  • Interleukin-1 / immunology
  • Interleukin-1 / metabolism*
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / immunology
  • Interleukin-17 / metabolism
  • Joints / immunology
  • Joints / pathology
  • Membrane Glycoproteins / immunology
  • Membrane Glycoproteins / metabolism*
  • Mice
  • RANK Ligand
  • RNA, Messenger / analysis
  • Receptor Activator of Nuclear Factor-kappa B
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Membrane / immunology
  • Synovial Membrane / metabolism
  • Tumor Necrosis Factor-alpha / biosynthesis


  • Carrier Proteins
  • Interleukin-1
  • Interleukin-17
  • Membrane Glycoproteins
  • RANK Ligand
  • RNA, Messenger
  • Receptor Activator of Nuclear Factor-kappa B
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha
  • Cathepsins
  • Cathepsin K
  • Ctsk protein, mouse