title: The changes in serum chemokines following leflunomide therapy in patients with rheumatoid arthritis.
abstract: We undertook this study to evaluate the effects of leflunomide, an oral pyrimidine synthesis inhibitor, on the serum chemokine levels in patients with active rheumatoid arthritis (RA) who were refractory to treatment with methotrexate (MTX) or did not tolerated MTX treatment. RA patients were supposed to receive leflunomide (100 mg/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 enzyme-linked immunosorbent assay before and after 3, 6, 9, and 12 months of treatment with leflunomide. 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 until 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 and IL-8 level with 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. Leflunomide, beside a clinical improvement, reduce serum chemokines concentrations in RA patients. Leflunomide seems to be an effective treatment for RA, alternative to current therapies.
authors.affiliation: Department of Rheumatology and Internal Diseases, Medical University of Bialystok, Bialystok, Poland. klimp@umwb.edu.pl
authors.forename: Piotr Adrian
authors.initials: PA
authors.lastname: Klimiuk
authors.forename: Jacek
authors.initials: J
authors.lastname: Kita
authors.forename: Justyna
authors.initials: J
authors.lastname: Chwiecko
authors.forename: Stanislaw
authors.initials: S
authors.lastname: Sierakowski
mesh_terms: D000328:Adult; D000368:Aged; D018501:Antirheumatic Agents / Q000627:therapeutic use*; D001172:Arthritis, Rheumatoid / Q000097:blood / Q000188:drug therapy* / Q000503:physiopathology; D018932:Chemokine CCL2 / Q000097:blood; D018946:Chemokine CCL5 / Q000097:blood; D018925:Chemokines / Q000097:blood*; D006304:Health Status; D006801:Humans; D015850:Interleukin-6 / Q000097:blood; D007555:Isoxazoles / Q000627:therapeutic use*; D007596:Joints / Q000503:physiopathology; D000077339:Leflunomide; D008875:Middle Aged; D012720:Severity of Illness Index
chemical_list: D018501:Antirheumatic Agents; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D018946:Chemokine CCL5; D018925:Chemokines; C508600:IL6 protein, human; D015850:Interleukin-6; D007555:Isoxazoles; D000077339:Leflunomide