Adenosine & methotrexate polyglutamate concentrations in patients w/ juvenile arthritis

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Adenosine and methotrexate polyglutamate concentrations in patients with

juvenile arthritis

http://rheumatology.oupjournals.org/cgi/content/abstract/44/1/74

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 vs 49.6 nmol/l in untreated controls. Mean EMTX was 215.56

nmol/l. No significant correlation was found between adenosine

concentrations and MTX dose or EMTX. Adenosine concentration did not

differ in clinical responders when compared with non-responders.

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.

Department of Paediatrics and Adolescent Medicine and Institute of

Inherited Metabolic Disorders, University in Prague, 1st Faculty

of Medicine and Department of Pharmacology, Faculty of Medicine,

University, Czech Republic.

Correspondence to: E-mail: Pavla.Dolezalova@...