Synovial nitric oxide concentrations are increased and correlated with serum levels in patients with active Behçet’s disease: a pilot study

Behçet’s disease (BD) is a relapsing immunoinflammatory vasculitis of unknown etiology characterized by endothelial dysfunction. Articular symptoms and signs are present in about 75% of cases and characterized by seronegative arthritis and nonspecific synovitis. We demonstrated that both serum and erythrocyte nitric oxide (NO^·) levels, the most abundant free radical in the body, were elevated in BD and associated with disease activity. This study further investigated NO^· levels in the synovial fluid and serum from patients with active and inactive BD. A total of 23 BD patients with articular involvement (14 men and 9 women) satisfying International Study Group criteria and 15 age- and sex-matched healthy control subjects (9 men and 6 women) undergoing elective arthroscopy were included in this case-control investigation. The synovial fluid and serum were obtained from BD patients and controls. Clinical and laboratory findings including neutrophil count and erythrocyte sedimentation rate (ESR) were used to classify BD patients as active (n=11) or inactive (n=12). Synovial as well as serum NO^· levels were compared between the groups and correlation analysis was performed. Acute phase reactant levels were significantly higher (for each, p<0.01) in BD patients than control subjects in the active period. The mean synovial NO^· level in active Behçet’s patients (mean±SD 76.61±11.95 μmol/l) was significantly higher than in inactive patients (46.16±8.89 μmol/l, p<0.001) and healthy control subjects (39.60±8.03 μmol/l, p<0.001). The difference between inactive patients and controls was not significant (p>0.05). Active BD patients had significantly higher serum NO^· levels (38.84±9.15 μmol/l) than inactive patients (30.91±5.88 μmol/l, p=0.018) and control subjects (28.86±5.91 μmol/l, p=0.002). In addition, synovial NO^· levels were positively correlated with serum levels (r²=0.621, p<0.001). Increased synovial NO^· levels in active BD patients probably reflect a nonspecific inflammatory process of the synovium and, therefore, arthralgia and arthritis as a common finding of BD.