Chronic therapy with recombinant tumor necrosis factor-alpha in autoimmune NZB/NZW F1 mice.
We studied the effects of recombinant murine tumor necrosis factor-alpha (TNF-alpha) on autoimmune disease in lupus-prone NZB/NZW F1 (B/W) mice. Treatment with TNF-alpha, begun after the onset of clinical disease, improved survival relative to control mice: at age 10 months, 92% of mice treated with TNF-alpha were alive compared with 42% of control mice (P less than 0.05). Administration of TNF-alpha delayed the progression of renal disease, but sustained therapy did not prevent the eventual development of severe nephritis. Despite the improvement in survival, treatment with TNF-alpha did not inhibit anti-dsDNA antibody production. However, it accelerated T lymphocytopenia and abolished natural killer cell activity. These observations suggest that TNF-alpha 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-alpha cannot be sustained indefinitely by chronic therapy.
Gordon
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Arthritis/Immunology Section, Veterans Administration Medical Center, San Francisco, California 94121.
Ranges
G E
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Greenspan
J S
JS
Wofsy
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D000818:Animals; D001323:Autoantibodies / Q000032:analysis; D001327:Autoimmune Diseases / Q000473:pathology / Q000628:therapy*; D001806:Blood Urea Nitrogen; D004247:DNA / Q000276:immunology; D004195:Disease Models, Animal; D005260:Female; D007167:Immunotherapy; D007668:Kidney / Q000276:immunology / Q000473:pathology; D007674:Kidney Diseases / Q000276:immunology / Q000473:pathology / Q000628:therapy; D007694:Killer Cells, Natural / Q000276:immunology; D008180:Lupus Erythematosus, Systemic / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D051379:Mice; D008817:Mice, Mutant Strains; D011994:Recombinant Proteins / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000627:therapeutic use*
D001323:Autoantibodies; D011994:Recombinant Proteins; D014409:Tumor Necrosis Factor-alpha; D004247:DNA