Imbalance in production between vascular endothelial growth factor and endostatin in patients with rheumatoid arthritis

Objective. To clarify whether synovial cell proliferation indicates an imba lance in production between angiogenic growth factors and angiogenesis inhi bitors in rheumatoid arthritis (RA), we investigated the production of basi c fibroblast growth factor (b-FGF) and vascular endothelial growth factor ( VEGF) as representative angiogenic growth factors and endostatin as a repre sentative angiogenesis inhibitor. Methods. The b-FGF VEGF, and endostatin levels in 90 samples of peripheral blood (PB) and 15 samples of joint fluid obtained from patients with RA and 30 samples of PB and 10 samples of joint fluid from patients without RA, i ncluding 20 patients with inflammatory arthritis without purulent arthritis , and 10 patients with osteoarthritis were measured by ELISA. VEGF and endo statin levels in blood samples from 22 patients with RA were measured at 2 points: before and 4 or 5 months after the commencement of medication. Results. The b-FGF and VEGF levels in the PB and joint fluid samples from p atients with RA were markedly elevated compared to samples from patients wi thout RA. In contrast, endostatin levels in PB and joint fluid samples fi o m patients with RA were almost the same as in the samples from patients wit hout RA. VEGF levels in blood samples obtained 4 or 5 months after the comm encement of medication (combination of prednisolone 5 mg/day and disease mo difying antirheumatic drugs: either bucillamine 100 mg/day or salazosulfapy ridine 1000 mg/day) were significantly decreased From 27.1 +/- 8.5 pg/ml in samples obtained before commencement of medication to 18.1 +/- 16.2 pg/ml. Endostatin levels in the corresponding samples were significantly increase d, from 31.5 +/- 7.0 to 57.1 +/- 12.8 pg/ml. Conclusion. Our results reveal significant differences in b-FGF and VEGF le vels in PB and joint fluid samples, but no difference in endostatin levels, between patients with RA and those without RA, suggesting that angiogenesi s in RA occurs as a result of an imbalance in production between angiogenic growth factors and angiogenesis inhibitors.