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Interleukin 17 is a T cell-derived cytokine that induces the release of pro-inflammatory mediators in a wide range of cell types. Recently, a subset of IL-17-producing T helper cells (Th17) distinct from Th1 and Th2 cells has been described, which constitutes a new T cell polarization state. Aberrant Th17 responses and overexpression of IL-17 have been implicated in a number of autoimmune disorders including rheumatoid arthritis and multiple sclerosis. Molecules blocking IL-17 such as IL-17-specific monoclonal antibodies have proved to be effective in ameliorating disease in animal models. Hitherto, active immunization targeting IL-17 is an untried approach. Herein we explore the potential of neutralizing IL-17 by active immunization using virus-like particles conjugated with recombinant IL-17 (IL-17-VLP). Immunization with IL-17-VLP induced high levels of anti-IL-17 antibodies thereby overcoming natural tolerance, even in the absence of added adjuvant. Mice immunized with IL-17-VLP had lower incidence of disease, slower progression to disease and reduced scores of disease severity in both collagen-induced arthritis and experimental autoimmune encephalomyelitis. Active immunization against IL-17 therefore represents a novel therapeutic approach for the treatment of chronic inflammatory diseases.

Original publication

DOI

10.1002/eji.200636658

Type

Journal article

Journal

Eur J Immunol

Publication Date

11/2006

Volume

36

Pages

2857 - 2867

Keywords

Animals, Arthritis, Experimental, Autoantibodies, Encephalomyelitis, Autoimmune, Experimental, Extremities, Female, Immunotherapy, Active, Interleukin-17, Mice, Mice, Inbred Strains, Protein Folding, Recombinant Proteins, Vaccines, Virosome