The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans

The Influence of Methotrexate on the Metabolism and Vascular Effects of Adenosine in Humans

In this study we aim to determine whether methotrexate influences the metabolism and vascular effects of adenosine in humans in vivo. Adenosine is an endogenous purine-nucleoside with potent anti-inflammatory effects. Also, adenosine receptor stimulation induces vasodilation, ischaemic preconditioning and many other cardiovacular effects. Previous animal studies have provided limited evidence that the anti-inflammatory effects of methotrexate are mediated by adenosine receptor stimulation. In this study, we aim to determine whether also in humans in vivo, methotretate influences endogenous adenosine. Therefore, 10 patients with inflammatory arthritis are treated with methotretxae (15 mg/week orally) for 12 weeks. Before and after treatment, vasodilation to the infusion of adenosine and dipyridamole into the brachial artery is assessed as biomarker for the endogenous adenosine concentration.

Also, blood is drawn for the determination of CRP, ESR, Adenosine deaminase activity adn homocysteine.

Inclusion Criteria:

• 18-75 year
• polyarthritis
• DAS score > 2.5

Exclusion Criteria:

• previous use of MTX
• concomitant use of dipyridamole/sulfazalasine
• Alcohol > 21 U/week
• elevated liver enzymes
• pregnancy, breast-feeding, asthma, renal insufficiency, thrombocytopenia, leucocytopenia