The role of T-cell interleukin-17 in conducting destructive arthritis: lessons from animal models

Arthritis Res Ther. 2005;7(1):29-37. doi: 10.1186/ar1478. Epub 2004 Nov 30.


Interleukin-17 (IL-17) is a T cell cytokine spontaneously produced by cultures of rheumatoid arthritis (RA) synovial membranes. High levels have been detected in the synovial fluid of patients with RA. The trigger for IL-17 is not fully identified; however, IL-23 promotes the production of IL-17 and a strong correlation between IL-15 and IL-17 levels in synovial fluid has been observed. IL-17 is a potent inducer of various cytokines such as tumor necrosis factor (TNF)-alpha, IL-1, and receptor activator of NF-kappaB ligand (RANKL). Additive or even synergistic effects with IL-1 and TNF-alpha in inducing cytokine expression and joint damage have been shown in vitro and in vivo. This review describes the role of IL-17 in the pathogenesis of destructive arthritis with a major focus on studies in vivo in arthritis models. From these studies in vivo it can be concluded that IL-17 becomes significant when T cells are a major element of the arthritis process. Moreover, IL-17 has the capacity to induce joint destruction in an IL-1-independent manner and can bypass TNF-dependent arthritis. Anti-IL-17 cytokine therapy is of interest as an additional new anti-rheumatic strategy for RA, in particular in situations in which elevated IL-17 might attenuate the response to anti-TNF/anti-IL-1 therapy.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Antirheumatic Agents / pharmacology
  • Antirheumatic Agents / therapeutic use
  • Arthritis, Experimental / drug therapy
  • Arthritis, Experimental / pathology
  • Arthritis, Experimental / physiopathology*
  • Arthritis, Rheumatoid / drug therapy
  • Arthritis, Rheumatoid / etiology*
  • Arthritis, Rheumatoid / pathology
  • Arthritis, Rheumatoid / physiopathology
  • Autoimmune Diseases / physiopathology
  • Bone and Bones / pathology
  • Carrier Proteins / physiology
  • Cartilage, Articular / pathology
  • Cytokines / biosynthesis
  • Cytokines / genetics
  • Gene Expression Regulation / physiology
  • Humans
  • Inflammation / physiopathology
  • Interleukin-17 / antagonists & inhibitors
  • Interleukin-17 / physiology*
  • Interleukins / physiology
  • Membrane Glycoproteins / physiology
  • Mice
  • Neutrophils / pathology
  • Osteoclasts / pathology
  • RANK Ligand
  • Rats
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Interleukin / physiology
  • Receptors, Interleukin-17
  • Species Specificity
  • Synovial Fluid / metabolism
  • T-Lymphocytes / metabolism*
  • Tumor Necrosis Factor-alpha / physiology


  • Antirheumatic Agents
  • Carrier Proteins
  • Cytokines
  • IL17RA protein, human
  • Il17ra protein, mouse
  • Interleukin-17
  • Interleukins
  • Membrane Glycoproteins
  • RANK Ligand
  • Receptor Activator of Nuclear Factor-kappa B
  • Receptors, Interleukin
  • Receptors, Interleukin-17
  • TNFRSF11A protein, human
  • TNFSF11 protein, human
  • Tnfrsf11a protein, mouse
  • Tnfsf11 protein, mouse
  • Tumor Necrosis Factor-alpha