Objectives: Methotrexate (MTX) is one of the most widely used disease-modifying antirheumatoid drugs in the treatment of juvenile rheumatoid arthritis (JRA). We studied its effect on the production of two proinflammatory cytokines, interleukin-6 (IL-6) and tumor necrosis factor alpha (TNFalpha), by peripheral blood cells in patients with JRA.
Methods: Interleukin-6 and TNFalpha levels were measured at 0 and 4 weeks in whole blood cultures with and without lipopolysaccharide (LPS) stimulation in 19 children treated with MTX (10 mg/m(2 )per week) or placebo. Ten healthy individuals were included as healthy controls.
Results: Spontaneous production of IL-6 and TNFalpha by peripheral blood cells of patients with JRA was higher than in healthy controls ( P<0.01). However, IL-6 and TNFalpha production after LPS stimulation was similar in healthy controls and patients. The two groups of patients, i.e., those treated with placebo and those treated with MTX, had similar spontaneous and induced IL-6 and TNFalpha production. At 4 weeks, the drop in spontaneous IL-6 and TNFalpha production was no different in the two groups, but LPS-stimulated IL-6 production was significantly lower in the MTX-treated group than the placebo group ( P<0.05).
Conclusion: Methotrexate reduces the production of IL-6 by activated cells, and this may be responsible for its anti-inflammatory property.