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Tumor necrosis factor-alpha (TNF-alpha) is critically involved in the pathogenesis of several chronic inflammatory diseases. Monoclonal antibodies against TNF-alpha are currently used for the treatment of rheumatoid arthritis and Crohn's disease. This report describes a simple and effective method for active immunization against self TNF-alpha. This vaccination approach leads to a T-cell-dependent polyclonal and sustainable anti-TNF-alpha autoantibody response that declines upon discontinuation of booster injections. The autoantibodies are elicited by injecting modified recombinant TNF-alpha molecules containing foreign immunodominant T-helper epitopes. In mice immunized with such molecules, the symptoms of experimental cachexia and type II collagen-induced arthritis are ameliorated. These results suggest that vaccination against TNF-alpha may be a useful approach for the treatment of rheumatoid arthritis and other chronic inflammatory diseases.

Original publication

DOI

10.1038/10878

Type

Journal article

Journal

Nat Biotechnol

Publication Date

07/1999

Volume

17

Pages

666 - 669

Keywords

Animals, Arthritis, Rheumatoid, Autoantibodies, Cachexia, Collagen, Epitopes, Immunization, Lymphocyte Activation, Male, Mice, Mice, Inbred BALB C, Mice, Inbred C3H, Mice, Inbred DBA, Neutralization Tests, Recombinant Proteins, T-Lymphocytes, Tumor Necrosis Factor-alpha