Kynurenic acid, an endogenous constituent of rheumatoid arthritis synovial fluid, inhibits proliferation of synoviocytes in vitro

Rheumatol Int. 2006 Mar;26(5):422-6. doi: 10.1007/s00296-005-0057-4. Epub 2005 Oct 12.

Abstract

Kynurenic acid is an antagonist of ionotropic glutamate receptors. It has been found that glutamate antagonists inhibit proliferation of different human tumor cells. Since the hyperplasia of synovial fibroblasts is one of the most striking features of inflammatory arthritis, the main goals of this study were detection and quantification of kynurenic acid in synovial fluid obtained from patients with rheumatoid arthritis, and determination of its effect on proliferation of synoviocytes in vitro. Presence of kynurenic acid was determined by HPLC in all 58 samples of synovial fluid. The mean concentration was 15.89 pmol/ml. Kynurenic acid inhibited synoviocyte proliferation with the IC50 value of 5.9 mM. In subthreshold concentration of 0.3 mM it enhanced antiproliferative action of celecoxib and nimesulide. In conclusion, the presence of kynurenic acid in synovial fluid was documented in patients with rheumatoid arthritis. Its potential role as an endogenous substance, controlling synoviocyte proliferation can be suggested.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arthritis, Rheumatoid / physiopathology*
  • Cell Proliferation*
  • Cells, Cultured
  • Female
  • Humans
  • Knee Joint / physiopathology*
  • Kynurenic Acid / analysis*
  • Kynurenic Acid / metabolism
  • Male
  • Rabbits
  • Synovial Fluid* / cytology
  • Synovial Fluid* / physiology

Substances

  • Kynurenic Acid