Adenosine and cytokine levels following treatment of rheumatoid arthritis with dipyridamole
- 153 Downloads
Adenosine can suppress the release of tumour necrosis factor-α (TNF-α) from activated monocytes and macrophages, and may contribute to the anti-inflammatory activities of methotrexate and sulphasalazine. Dipyridamole inhibits the cellular uptake and metabolism of adenosine and we have, therefore, examined the effects of dipyridamole in patients with rheumatoid arthritis in an attempt to alleviate their symptoms. Forty patients aged 18–75 years were randomised to receive dipyridamole 400 mg/day or placebo. Blood samples were taken at baseline and at monthly intervals for 6 months. Purines were determined by HPLC and cytokines by ELISA. After 3 months of treatment there were significant reductions in neopterin levels and in the modified Health Assessment Questionnaire score, but these were not maintained. Dipyridamole had no effect on disease severity or the levels of purine metabolites, interleukin-1β (IL-1β), IL-6, TNF-α, lipid peroxidation products, erythrocyte sedimentation rate or C-reactive protein. In conclusion, rheumatoid arthritis patients showed no clinical improvement following treatment with dipyridamole for 6 months.
KeywordsAdenosine Dipyridamole Rheumatoid arthritis TNF-α IL-1β IL-6
We are grateful to the NHS R&D Levy, the Peacock Foundation and the Denbies Trust for financial support. We would like to thank Rosalind McMillan and Nicole Packham for technical assistance.
- 1.Feldmann M (1996) The cytokine network in rheumatoid arthritis: definition of TNF-α as a therapeutic target. J R Coll Phys Lond 30:560–570Google Scholar
- 7.Bshesh K, Zhao B, Spight D, Biaggioni I, Feokistov I, Denenberg A, Wong HR, Shanley TP (2002) The A2A receptor mediates an endogenous regulatory pathway of cytokine expression in THP-1 cells. J Leuk Biol 72:1027–1036Google Scholar
- 16.Salmon HE, Cronstein BN (1990) Fcγ receptor-mediated functions in neutrophils are modulated by adenosine receptor occupancy: A1 receptors are stimulatory and A2 receptors are inhibitory. J Immunol 145L:2235–2240Google Scholar
- 18.Arnett FC, Edworthy SM, Bloch DA, Mcshane DJ, Fries JF, Cooper NS, healey LA, Kaplan SR, Liang MH, Luthra HS, Medsger TA, Mitchell DM, Neustadt DH, Pinals RS, Schaller JG, Sharp JT, Wilder RL, Hunder GG (1988) The American-rheumatism-association 1987 revised criteria for the classification of rheumatoid-arthritis. Arthritis Rheum 31:315–324PubMedGoogle Scholar
- 21.ICSH (1933) ICSH Recommendations for measurement of erythrocyte sedimentation rate. Clin Pathol 46:198–200Google Scholar
- 22.Westergren A (1921) Studies of the suspension stability of the blood in pulmonary tuberculosis. Med Scand 54:247–250Google Scholar