Rheumatology: Current Research
Open Access

Abstract

The Effect of Methotrexate and Leflunomide on the Cytokine Profile and Nitric Oxide Metabolism in Rheumatoid Arthritis Patients

Dubikov AI, Medved EE and Belogolovykh LA

Objective: To reveal the role of individual cytokines and nitric oxide in pharmacological effects of methotrexate and leflunomide in rheumatoid arthritis (RA) patients. Materials and methods: Ninety four patients with confirmed seropositive RA aged 20-60 yrs were examined. The patients were separated into groups of early and late RA and of “erosive” and “non-erosive” RA. 63 patients received methotrexate, and 31, leflunomide. The levels of IL-1β, IL-6, IL-10, and TNF-α were determined in blood serum and synovial fluid using solid-phase enzyme immunoassay. The levels of NO2 and NO3 were determined in blood serum, synovial fluid, and urine by spectrophotometry. All analyses were performed both before and 6 months post therapy. Therapy effectiveness was estimated in the same period. Results: The levels of NO metabolites and cytokines except for IL-6 were increased in synovial fluid and urine of all patients compared to the control. The methotrexate therapy resulted in an increase in IL-1, TNF, and NO metabolites in the peripheral blood. As distinct from methotrexate, leflunomide strongly suppressed IL-6 production in blood serum. The therapy using either drug resulted in a manifold decrease in the levels of IL-1, TNF, and NO metabolites in synovial fluid. Conclusions: There were opposite changes of levels of cytokines and NO metabolites in RA patient’s blood and synovial fluid receiving methotrexate and leflunomide respectively.