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Since neovascularization plays an important role in the propagation of rheumatoid synovitis, we analyzed the concentration of gliostatin/platelet-derived endothelial cell growth factor (GLS/PD-ECGF), a potent angiogenic and chemotactic factor, in the synovial fluid and serum of rheumatoid arthritis (RA) patients. The immunoreactive GLS/PD-ECGF concentrations (mean value +/- S.D.) in synovial fluid, measured by a sandwich enzyme immunoassay, were significantly higher in RA patients than in osteoarthritis (OA) patients (233.02 +/- 219.40 vs. 9.09 +/- 14.86 ng/g, P < 0.001), and the serum concentrations were also higher in RA patients than in age-matched controls (8.77 +/- 7.60 vs. 3.74 +/- 2.61 ng/ml, P < 0.005). These results suggest that GLS/PD-ECGF may participate in the endothelial proliferation resulting in initiation of the extensive emigration of mononuclear cells and proliferation of the synovial tissues in rheumatoid arthritis, and that the immunoreactive GLS/PD-ECGF in serum as well as synovial fluids may be a useful diagnostic marker of RA.

The immuno-reactive human epidermal growth factor (h-EGF) level, measured by a sensitive enzyme immunoassay, was significantly higher in synovial fluids or synovial tissue extracts from 89 patients with rheumatoid arthritis (RA) than in those from 53 patients with osteoarthritis. RA synovial immuno-reactive h-EGF was predominantly of a low molecular weight form (LMW h-EGF) on gel filtration chromatography. Furthermore, in the RA group, the synovial immuno-reactive h-EGF correlated positively with C-reactive protein, an acute-phase reactant, in the blood examination and with synovial immunoglobulin M. These results suggest that synovial h-EGF is specifically produced by RA synovium from the initial stage of arthritis, and that the measurement of synovial h-EGF serves as an early indicator to appraise the RA activity. A pathogenesis of RA including growth factors and growth inhibitory factors are discussed.