REDUCTION OF LEUKOCYTE AND INTERLEUKIN-1-BETA CONCENTRATIONS IN THE SYNOVIAL-FLUID OF RHEUMATOID-ARTHRITIS PATIENTS TREATED WITH METHOTREXATE

Objective. To examine the effect of methotrexate (MTX) on the numbers of leukocytes in the peripheral blood (PB) and synovial fluid (SF) of patients with active rheumatoid arthritis (RA). Methods. Twelve patien ts were treated with MTX; 5 patients not taking MTX served as controls . Samples of PB and SF were collected at 0, 1, 4, and 8 weeks of the s tudy. Disease activity was scored, and total leukocytes, neutrophils, lymphocytes, and CD4+, CD8+, DR+, and CD25+ lymphocyte subsets were an alyzed in PB and SF. Interleukin-1beta (IL-1beta) concentrations in SF were determined. Results. Patients treated with MTX showed significan t clinical improvement. No change in PB leukocytes or lymphocyte subse ts was observed in either patient group over the 8-week study period. In contrast, the number of leukocytes, the number and proportion of ne utrophils, and the concentration of IL-1beta in the SF of patients tre ated with MTX were reduced. In addition, in MTX-treated patients, ther e was an appreciable decrease in SF CD8+ lymphocytes, but not CD4+, DR +, or CD25+ lymphocytes. Conclusion. These findings suggest that in RA , MTX acts, at least in part, by reducing the migration of leukocytes into the inflamed synovium. Local reduction of IL-1beta secretion may contribute to this effect.