Increased nitric oxide levels in patients with rheumatoid arthritis

Objectives. We determined whether serum levels of nitric oxide (NO) correlate with disease activity of rheumatoid arthritis (RA) and inflammatory cytokines by measuring the serum and synovial fluid (SF) concentrations of NO in patients with RA and patients with osteoarthritis (OA) and healthy subjects. Methods. The concentration of NO in each sample was determined by chemiluminescence. Cytokine levels were determined using sandwich enzyme-linked immunoassays. Results. The mean serum concentration 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 concentration of NO (3218 +/- 73.7, p < 0.01) was significantly higher than that of serum in patients with RA. Furthermore, levels of serum NO, interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNF-alpha) were significantly higher in patients with RA with active disease compared to patients with inactive disease. Serum NO levels correlated significantly with the morning joint stiffness, the number of tender or swollen 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 immunoregulation in the joints of patients with RA.