Chronic therapy with recombinant tumor necrosis factor-α in autoimmune NZB/NZW F 1 mice

Abstract

We studied the effects of recombinant murine tumor necrosis factor-α (TNF-α) on autoimmune disease in lupus-prone NZB/NZW F 1 (B/W) mice. Treatment with TNF-α, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-α were alive compared with 42% of control mice ( P < 0.05). Administration of TNF-α delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the imporvement in survival, treatment with TNF-α did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-α may retard murine lupus in B/W mice through effects on cellular rather than humoral mechanisms. Our findings also indicate that the beneficial effects of TNF-α cannot be sustained indefinitely by chronic therapy.