Effect of methotrexate on blood purine and pyrimidine levels in patients with rheumatoid arthritis

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