ROLE OF TUMOR-NECROSIS-FACTOR-ALPHA AND PLATELET-ACTIVATING-FACTOR INNEOANGIOGENESIS INDUCED BY SYNOVIAL-FLUIDS OF PATIENTS WITH RHEUMATOID-ARTHRITIS

The aim of the present study was to investigate in vivo in a mouse mod el the stimulation of neoangiogenesis by synovial fluids of patients w ith rheumatoid arthritis (RA) and to determine the role of tumor necro sis factor (TNF)-alpha and platelet-activating factor (PAF) in the for mation of new vessels. Angiogenesis was studied in a mouse model in wh ich Matrigel, injected subcutaneously, was used as a vehicle for tile delivery of potential angiogenic stimuli. Synovial fluids of patients with RA but not with osteoarthritis (OA) were shown to induce neoangio genesis. Since synovial fluid of patients with RA contained significan tly higher levels of TNF-alpha-like bioactivity and of PAF than that o f patients with OA, the role of these mediators was evaluated by using an anti-TNF-alpha neutralizing monoclonal antibody (mAb) and a PAF re ceptor antagonist, WEB 2170. When added to Matrigel, anti-TNF-alpha mA b and particularly WEB 2170 significantly reduced neoangiogenesis indu ced by synovial fluids of RA patients. Moreover, PAF extracted and pur ified from synovial fluid induced angiogenesis. These results suggest that the neoangiogenesis observed in rheumatoid synovitis may be due, at least in part, to the angiogenic effect of locally produced TNF-alp ha and PAF.