Background Chemokines play an important role in the pathogenesis of rheumatoid arthritis (RA).
Objectives We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokines levels in patients with active rheumatoid arthritis, who were refractory to treatment with MTX or did not tolerated MTX treatment.
Methods RA patients were supposed to receive leflunomide (100mg/day loading dose for 3 days followed by 20 mg/day orally for the 12 months). Serum concentrations of RANTES (regulated upon activation, normal T cell expressed and secreted), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 (IL-8) were assessed by ELISA before and after 3, 6, 9 and 12 months of treatment with leflunomide.
Results Three months therapy with leflunomide caused reduction in serum RANTES and MCP-1 (in both cases p<0.001) levels. Decrease in the concentration of these chemokines persisted till the end of the study period, but was less significant. In the case of IL-8 its serum levels significantly diminished after 6 months of therapy with leflunomide (p<0.01), and remained stable to the end of the study. Changes in serum chemokine levels were accompanied by significant decrease of disease activity score (DAS) (p<0.001). Prior to the first dose of leflunomide serum concentrations of studied chemokines correlated with marker of RA activity such as the erythrocyte sedimentation rate (ESR) and IL-8 level with disease activity score (DAS). Furthermore, we demonstrated significant correlations between serum levels of RANTES, MCP-1 and IL-8. During study period such associations were far less or not significant.
Conclusions Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for rheumatoid arthritis, alternative to current therapies.
Disclosure of Interest None Declared
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