Rheumatology 1999; 38: 997-1002
© 1999 British Society for Rheumatology
Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis
. Smole
skaski1
Rheumatology Hospital, Sopot,
1 Department of Biochemistry, Medical University, Gdask, Poland and
2 Purine Research Laboratory, Guy's Hospital, London, UK
Correspondence to:
R. T. Smoleski, Department of Biochemistry, Medical University of Gdask, 80-211 Gdask, Debinki 1, Poland.
Objective. The mechanism of anti-inflammatory effects of methotrexate (MTX) at low dose may relate to a decrease in availability of the purine precursor or it may depend on accumulation of 5-aminoimidazole-4-carboxamide (AICAR) and the anti-inflammatory nucleoside adenosine. The aim of this study was to evaluate the possible mechanism of action by analysis of changes in blood concentrations of purine and pyrimidine metabolites during MTX treatment.
Methods. Venous blood samples were collected from rheumatoid arthritis patients before and at different times for up to 7 days after the start of MTX treatment. Whole blood concentrations of adenosine, uridine, hypoxanthine, uric acid and erythrocyte nucleotides were measured by HPLC.
Results. The initial blood adenosine concentration was 0.073 ± 0.013 µM and no differences were observed during MTX treatment. However, a decrease in uric acid concentration was observed from 205.5±13.5 to 160.9±13.5 µM (P<0.05) within 24 h after MTX administration. The hypoxanthine concentration decreased in parallel with uric acid, while the uridine concentration decreased 48 h after MTX administration. No accumulation of AICAR-triphosphate (ZTP) was observed in the erythrocytes.
Conclusions. MTX decreases circulating purine and pyrimidine concentrations, and their availability for DNA and RNA synthesis, which may affect immune cell proliferation and protein (cytokine) expression. The absence of adenosine concentration changes and lack of ZTP formation is evidence against an AICAR/adenosine mechanism, although localized adenosine concentration changes cannot be excluded.
KEY WORDS: Methotrexate, Rheumatoid arthritis, Adenosine, Uric acid, Purines, Pyrimidines.
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  N P Riksen, P Barrera, P H H van den Broek, P L C M van Riel, P Smits, and G A Rongen Methotrexate modulates the kinetics of adenosine in humans in vivo Ann Rheum Dis, April 1, 2006; 65(4): 465 - 470. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. Dolezalova, J. Krijt, J. Chladek, D. Nemcova, and J. Hoza Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis Rheumatology, January 1, 2005; 44(1): 74 - 79. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. Gerards, S. de Lathouder, E. R. de Groot, B. A. C. Dijkmans, and L. A. Aarden Inhibition of cytokine production by methotrexate. Studies in healthy volunteers and patients with rheumatoid arthritis Rheumatology, October 1, 2003; 42(10): 1189 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M CUTOLO, A SULLI, C PIZZORNI, B SERIOLO, and R H STRAUB Anti-inflammatory mechanisms of methotrexate in rheumatoid arthritis Ann Rheum Dis, August 1, 2001; 60(8): 729 - 735. [Full Text] [PDF]
|
|