Background Adenosine exerts strong anti-inflammatory effects.
In vitro and animal studies suggest that adenosine release is implicated in the mechanism of action of methotrexate (MTX) and sulfasalazine. Whether blocking TNF has any effect on this pathway has not been investigated yet.
Objectives To assess the short anf mid-term effect of MTX and anti-TNF therapy on the circulating levels of adenosine and aminoimidazolcarboximide ribotide (AICAR) in rheumatoid arthritis (RA).
Methods Patients starting therapy with MTX (n = 10; dose 15 mg/kg im) or infliximab (n = 10, dose 3 mg/kg) were enrolled in the study. Blood samples were drawn immediately before and 2, 6, 24 and 48 h and 4 weeks after the first administration of MTX or anti-TNF. Measurements before and 2 and 6 h after administration were also performed on week 12. To avoid adenosine degradation, blood was directly mixed with a solution containing EHNA 10 μM, dipyridamole 20 μM and indomethacin 2 mg/L. Adenosine and AICAR were measured using sensitive HPLC methods. Response to therapy was assessed at week 4 and 12 using the EULAR criteria.
Results Baseline adenosine levels were similar in both patient groups (median, [p25 – p75] 213 [146 – 302] and 230 [71 – 291] nmol/L for MTX and anti-TNF respectively). Adenosine levels showed marked inter- and intra-individual variability (75% and 49% respectively). In 3 patients, adenosine concentrations raised markedly 2 h after the first MTX dose. Nevertheless, no consistent changes were observed in the whole MTX group or after anti-TNF administration.
Within the study period, 55% and 64% of the patients receiving MTX and anti-TNF showed clinical response. The latter was also not reflected in the levels of adenosine. AICAR could not be detected in any of the samples.
Conclusion In patients with RA, neither MTX therapy nor its effectivity are mirrored by consistent changes in circulating adenosine levels. The same holds true for anti-TNF treatment. This does not exclude the possibility of a modulation of adenosine release at the target organ.