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Adenosine and methotrexate polyglutamate concentrations in patients with juvenile arthritis

P Dolezalová1, J Krijt, J Chládek

  • 1Department of Paediatrics and Adolescent Medicine, 1st Faculty of Medicine, Charles University in Prague, Ke Karlovu 2, 128 08 Prague 2, Czech Republic. Pavla.Dolezalova@lf1.cuni.cz

Rheumatology (Oxford, England)
|September 30, 2004
PubMed
Abstract

Insights

Methotrexate (MTX) treatment in juvenile idiopathic arthritis (JIA) does not increase blood adenosine levels. Erythrocyte MTX polyglutamate levels did not correlate with adenosine, suggesting local adenosine release at inflamed tissues may mediate MTX's anti-inflammatory effects.

Area of Science:

  • Rheumatology
  • Pharmacology
  • Biochemistry

Background:

  • Methotrexate (MTX) is a cornerstone therapy for rheumatic diseases, with its anti-inflammatory effects potentially mediated by adenosine.
  • Adenosine's accumulation is thought to result from intracellular MTX polyglutamates (EMTX).
  • This study investigates the relationship between adenosine, EMTX, and treatment efficacy in pediatric rheumatic disease.

Purpose of the Study:

  • To measure adenosine concentrations in children with juvenile idiopathic arthritis (JIA) receiving MTX compared to controls.
  • To correlate adenosine levels with erythrocyte MTX polyglutamate (EMTX) concentrations.
  • To assess the relationship between adenosine levels and therapeutic response in JIA patients.

Main Methods:

  • Adenosine and EMTX concentrations were measured in erythrocytes of 30 JIA patients on long-term MTX and 16 controls.
  • Adenosine was quantified using liquid chromatography/tandem mass spectrometry (LC-MS/MS).
  • EMTX was determined via enzymatic assay, and therapeutic efficacy was evaluated using JIA improvement criteria.

Main Results:

  • No significant difference in mean blood adenosine concentrations was observed between MTX-treated JIA patients (48.05 nmol/l) and controls (49.6 nmol/l).
  • No significant correlation was found between adenosine levels and MTX dose or EMTX concentrations (P=0.8 and P=0.6, respectively).
  • Adenosine concentrations did not differ between clinical responders and non-responders (P=0.9).

Conclusions:

  • Effective MTX dose, indicated by EMTX, does not impact systemic blood adenosine concentrations in JIA patients.
  • If adenosine mediates MTX's anti-inflammatory action, it likely occurs via local release at inflamed tissues.
  • Systemic blood adenosine levels may not reflect the localized anti-inflammatory mechanisms of MTX in JIA.

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