INCREASED NITRIC-OXIDE LEVELS IN PATIENTS WITH RHEUMATOID-ARTHRITIS

Objectives. We determined whether serum levels of nitric oxide (NO) co rrelate with disease activity of rheumatoid arthritis (RA) and inflamm atory cytokines by measuring the serum and synovial fluid (SF) concent rations of NO in patients with RA and patients with osteoarthritis (OA ) and healthy subjects. Methods. The concentration of NO in each sampl e was determined by chemiluminescence. Cytokine levels were determined using sandwich enzyme-linked immunoassays. Results. The mean serum co ncentration of NO was significantly higher in patients with RA (293.4 +/- 108.5 nM) compared with that of patients with OA (33.4 +/- 4.0, p < 0.01) and healthy subjects (35.9 +/- 4.5, p +/- 0.01). The mean SF c oncentration of NO (3218 +/- 73.7, p < 0.01) was significantly higher than that of serum in patients with RA. Furthermore, levels of serum N O, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) we re significantly higher in patients with RA with active disease compar ed to patients with inactive disease. Serum NO levels correlated signi ficantly with the morning joint stiffness, the number of tender or swo llen joints, and CRP. Furthermore, NO levels correlated significantly with serum TNF-alpha and IL-6 levels. Conclusions. Our results suggest that increased endogenous NO synthesis reflects abnormalities of immu noregulation in the joints of patients with RA.