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Rheumatology Advance Access originally published online on September 28, 2004
Rheumatology 2005 44(1):74-79; doi:10.1093/rheumatology/keh401
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Rheumatology Vol. 44 No. 1 © British Society for Rheumatology 2004; all rights reserved

PAPER

Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis

P. Dolezalová, J. Krijt1, J. Chládek2, D. Nemcová and J. Hoza

Department of Paediatrics and Adolescent Medicine and 1 Institute of Inherited Metabolic Disorders, Charles University in Prague, 1st Faculty of Medicine and 2 Department of Pharmacology, Faculty of Medicine, Charles University, Hradec Králové, Czech Republic.

Correspondence to: P. Dolezalová, Department of Paediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University in Prague, Ke Karlovu 2, 128 08 Prague 2, Czech Republic. E-mail: Pavla.Dolezalova{at}lf1.cuni.cz

Objective. In contrast to the anti-proliferative properties of high-dose methotrexate (MTX) its anti-inflammatory mechanism of action in rheumatic diseases has been attributed to increased adenosine accumulation, most likely caused by long-lived intracellular MTX polyglutamates. The aim of this study was to assess adenosine concentrations in MTX-treated and untreated children and to relate it to MTX polyglutamate concentration measured in erythrocytes and to the therapeutic efficacy.

Methods. Adenosine and MTX-polyglutamate concentrations in erythrocytes (EMTX) were assessed in venous blood samples taken before the next MTX dose in 30 patients treated long-term for juvenile idiopathic arthritis (JIA) and in 16 untreated matched controls. The blood concentration of adenosine was measured by the liquid chromatography/tandem mass spectrometry (LC-MS/MS) method and EMTX by an enzymatic assay. Therapeutic efficacy was assessed using the preliminary definition of improvement in JIA patients.

Results. Mean blood adenosine concentration in MTX-treated patients was 48.05 nmol/l (S.D. 10.1) vs 49.6 nmol/l (S.D. 12.5) in untreated controls (P = 0.55). Mean EMTX was 215.56 nmol/l (S.D. 212.9). No significant correlation was found between adenosine concentrations and MTX dose or EMTX (P = 0.8 and 0.6, respectively). Adenosine concentration did not differ in clinical responders when compared with non-responders (P = 0.9).

Conclusions. We have shown that there is no impact of effective MTX dose represented by EMTX on blood adenosine concentration in JIA patients. If MTX anti-inflammatory action is mediated by adenosine it is likely that local release of adenosine at inflamed tissues is responsible for its action which may not be reflected by sustained increase of its blood concentration.

KEY WORDS: Adenosine, Methotrexate polyglutamates, Juvenile arthritis


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