Plasma and rectal adenosine in inflammatory bowel disease: Effect of methotrexate

In animal models, the antiinflammatory mechanism of action of methotrexate has been attributed to elevation of the extracellular concentration of the endogenous autocoid, adenosine. Our goal was to determine if methotrexate e levates adenosine concentrations in plasma and at the site of disease in pa tients with inflammatory bowel disease. In 10 patients with Crohn's disease or ulcerative colitis, rectal adenosine and plasma adenosine concentration s were measured before and immediately after a subcutaneous injection of me thotrexate, 15 or 25 mg. The mean predose rectal adenosine concentration of 2.4 mu mol/l was not significantly different from the postdose concentrati on of 2.1 mu mol/l, p = 0.17, (paired two-tailed t test). Rectal adenosine concentration tended to correlate with rectal endoscopic disease activity, r = 0.59, p = 0.067 (Spearman rank order correlation). After methotrexate i njection, neither the mean daily plasma adenosine concentration, nor the pl asma adenosine at any individual time point, were significantly different f rom preinjection values. In patients with inflammatory bowel disease, an in jection of methotrexate in the clinically effective dose range does not rai se rectal or plasma adenosine concentrations. A role for adenosine as the m ediator of the antiinflammatory action of methotrexate is not supported.