Vascular endothelial growth factor levels are increased and associated with disease activity in patients with Behcet's syndrome

Background/aims Vascular endothelial growth factor (VEGF) is a cytokine participating in inflammation with potent endothelial cell effects. It is produced by macrophages, neutrophils and vascular endothelial cells and can alter vessel permeability. Behcet's syndrome is a systemic inflammatory disorder with unknown etiology. Vascular endothelial dysfunction is one of the prominent features of the disease. We previously demonstrated the possible involvement of proinflammatory cytokines [tumor necrosis factor (TNF)-alpha, soluble interleukin-2 receptor (sIL-2R), interleukin (IL)-6 and IL-8], nitric oxide (NO) and adrenomedullin in the etiopathogenesis of Behcet's syndrome. Since VEGF expression is induced by these cytokines and VEGF itself is a potent stimulator of NO production with endothelial cell effects, this study aimed to investigate whether VEGF was affected during the course of Behcet's syndrome. We also assessed the possible involvement of VEGF in ocular Behcet's syndrome or in disease activity. Methods This multicenter case-control study included a total of 39 patients with active (n = 22) or inactive (n = 17) Behcet's syndrome (mean age, 38.1 +/- 10.4 years; 21 men and 18 women) satisfying International Study Group criteria, and 15 healthy hospital-based control volunteers (mean age, 39.2 +/- 9.3 years; eight men and seven women) matched for age and gender from a similar ethnic background. Patients were examined by a dermatologist and an ophthalmologist with an interest in Behcet's syndrome. Plasma VEGF concentrations were measured using a newly established enzyme-linked immunosorbent assay. Clinical findings and acute-phase reactant parameters such as erythrocyte sedimentation rate, alpha(1)-antitrypsin, alpha(2)-macroglobulin, and neutrophil count were used to classify the disease in Behcet's patients as active or inactive. The Wilcoxon test or the Mann-Whitney U-test was used for statistical analysis as indicated and the results were expressed as mean +/- SD, with range. Results The mean plasma VEGF level in patients with Behcet's syndrome (291.9 +/- 97.1 pg/mL; range 121-532 pg/mL) was higher than that in control subjects (103.0 +/- 43.6 pg/mL; range 25-187 pg/mL) and the difference was significant (P < 0.001). Patients with active disease had significantly (P < 0.001) higher VEGF levels than patients with inactive disease (347.6 +/- 87.1 vs. 219.9 +/- 51.6 pg/mL). In addition, ocular Behcet's patients (n = 23) had higher VEGF levels (315.7 +/- 92.1 pg/mL) than nonocular patients (n = 16, 257.8 +/- 96.6 pg/mL) and the difference was of borderline significance (P = 0.041). The levels of all acute-phase reactant parameters were significantly higher in the active stage than in the inactive stage (for each, P < 0.01) or in control subjects (for each, P < 0.001). Conclusions VEGF may participate in the course of Behcet's syndrome, especially in the active stage, and elevated levels of VEGF may be an additional risk factor for the development of ocular disease, contributing to poor visual outcome.