Antiinflammatory effect of A3 adenosine receptor agonists in murine autoimmune arthritis models

J Rheumatol. 2005 Mar;32(3):469-76.


Objective: CF101, an A3 adenosine receptor (A3AR) agonist, is a small orally bioavailable molecule known to suppress in vitro the production of tumor necrosis factor-alpha (TNF-alpha). We evaluated its therapeutic potential and antiinflammatory effects in 3 murine models of adjuvant induced arthritis (AIA).

Methods: The antiinflammatory effect of CF101 was examined in rat AIA, in mouse collagen induced arthritis, and in tropomyosin induced arthritis. The clinical effect of another A3AR agonist, Cl-IB-MECA, was examined in rat AIA. The effect of low dose (10 or 100 mg/kg/day) A3AR agonists administered orally once daily on arthritis severity was assessed clinically and histologically. The effect of CF101 on the protein expression level of TNF-alpha in the synovial tissue, draining lymph nodes, and spleen cells was determined by Western blot.

Results: CF101 and Cl-IB-MECA markedly ameliorated the clinical and histological features of arthritis in the 3 models when administered orally at a low dose of 10 mg/kg body weight in the 3 autoimmune arthritis models. The lower dose of 10 mg/kg of either CF101 or Cl-IB-MECA had better antiinflammatory effect than the higher 100 mg/kg dose. Decreased expression of TNF-alpha was noted in protein extracts of synovia, draining lymph nodes, and spleen tissues.

Conclusion: The results provide evidence that A3AR agonists exert significant antirheumatic effects in different autoimmune arthritis models by suppression of TNF-alpha production. The beneficial activity of the drugs at the low dose demonstrates that the effect is A3AR mediated.

MeSH terms

  • Adenosine / analogs & derivatives*
  • Adenosine / pharmacology
  • Adenosine / therapeutic use*
  • Adenosine A3 Receptor Agonists*
  • Adenosine A3 Receptor Antagonists
  • Animals
  • Anti-Inflammatory Agents / pharmacology
  • Anti-Inflammatory Agents / therapeutic use*
  • Arthritis, Experimental / drug therapy*
  • Arthritis, Experimental / pathology
  • Collagen / immunology
  • Dose-Response Relationship, Drug
  • Female
  • Joints / drug effects
  • Joints / immunology
  • Joints / pathology
  • Lymph Nodes / immunology
  • Male
  • Mice
  • Mice, Inbred DBA
  • Quinazolines / pharmacology
  • Rats
  • Receptor, Adenosine A3 / metabolism*
  • Spleen / immunology
  • Triazoles / pharmacology
  • Tumor Necrosis Factor-alpha / metabolism


  • 9-chloro-2-(2-furyl)-5-phenylacetylamino(1,2,4)triazolo(1,5-c)quinazoline
  • Adenosine A3 Receptor Agonists
  • Adenosine A3 Receptor Antagonists
  • Anti-Inflammatory Agents
  • CF101
  • Quinazolines
  • Receptor, Adenosine A3
  • Triazoles
  • Tumor Necrosis Factor-alpha
  • Collagen
  • Adenosine