Serum Cytotoxic Factor and its' Inhibitorin Rheumatoid Arthritis.

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The peripheral blood serum of patients with severe active rheumatoid arthritis (RA) was found to have a cytotoxic effect on autologous mononuclear cells. The cytotoxic factor was partially purified and shown to have a molecular weight of about 900 kd, using gel filtration. The factor differed from cytokines such as tumor necrosis factor-alpha (TNF-alpha) and also differed from complement components. It also differed from hydrolytic enzyme such as protease, collagenase, and phospholipase A_2. It destroyed normal peripheral blood mononuclear cells in vitro at the same concentration as it found in vivo, and also nonspecifically destroyed such human cell lines as CCRF-CEM, Raji, U-937, and HL-60. Each RA patient with this serum cytotoxic factor had severe systemic tissue disease as well as rapid and severe destruction of most joints. Thus, we have identified a cytotoxic factor in RA serum which causes systemic tissue damage. And we also partially pirified the inhibitor against the cytotoxic factor, using gel filtration.