Function of interleukin-20 as a proinflammatory molecule in rheumatoid and experimental arthritis

Arthritis Rheum. 2006 Sep;54(9):2722-33. doi: 10.1002/art.22039.


Objective: The pathogenesis of rheumatoid arthritis (RA) reflects an ongoing imbalance between proinflammatory and antiinflammatory cytokines. Interleukin-20 (IL-20) has proinflammatory properties for keratinocytes. In this study, we sought to determine whether IL-20 is involved in RA.

Methods: We analyzed IL-20 levels in synovial fluid from RA patients. IL-20 and its receptors were detected in RA synovial fibroblasts (RASFs), using immunohistochemical staining. The effect of IL-20 on endothelial cells, neutrophils, and RASFs was investigated using MTT and migration assays. The expression of IL-20 and its receptors in healthy rats and in rats with collagen-induced arthritis (CIA) was also analyzed. Soluble IL-20 receptor type I (sIL-20RI) or sIL-20RII was administered to rats with CIA by intramuscular electroporation, and the severity of arthritis was monitored.

Results: RA patients expressed significantly higher levels of synovial fluid IL-20 than did the rheumatic disease controls. IL-20 and its receptors were expressed in the synovial membranes and RASFs. IL-20 induced RASFs to secrete monocyte chemoattractant protein 1, IL-6, and IL-8, and it promoted neutrophil chemotaxis, RASF migration, and endothelial cell proliferation. Both IL-20 and IL-20RI were up-regulated in the rat CIA model. In vivo, electroporated sIL-20RI plasmid DNA decreased the severity of arthritis in the rats with CIA.

Conclusion: IL-20 was up-regulated in the synovial fluid of RA patients and acted as a chemokine that attracted the migration of neutrophils and RASFs in vitro. The rat CIA model demonstrated that IL-20 was involved in the pathogenesis of arthritis, because sIL-20RI significantly reduced arthritis in rats with CIA. Thus, IL-20 may modulate the incidence and severity of arthritis and play important roles at local sites of inflammation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Experimental / blood
  • Arthritis, Experimental / immunology*
  • Arthritis, Rheumatoid / blood
  • Arthritis, Rheumatoid / immunology*
  • Biomarkers / blood
  • Cell Culture Techniques
  • DNA, Complementary / genetics
  • Endothelium, Vascular / immunology
  • Fibroblasts / drug effects
  • Fibroblasts / immunology
  • Humans
  • Inflammation / blood
  • Interleukin-10 / blood*
  • Interleukins / genetics
  • Mice
  • Osteoarthritis / blood
  • Osteoarthritis / immunology
  • Rats
  • Reference Values
  • Reverse Transcriptase Polymerase Chain Reaction
  • Synovial Fluid / cytology
  • Synovial Fluid / immunology
  • Umbilical Veins


  • Biomarkers
  • DNA, Complementary
  • Interleukins
  • Interleukin-10
  • interleukin 20