Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis

Harald H. Hofstetter, Saleh M. Ibrahim, Dirk Koczan, Niels Kruse, Andreas Weishaupt, Klaus V. Toyka, Ralf Gold*

*Corresponding author for this work
    346 Citations (Scopus)

    Abstract

    Experimental autoimmune encephalomyelitis (EAE) is widely regarded as an animal model of the human disease multiple sclerosis. A multitude of studies has investigated the neuroantigen-specific T-cell mediated cytokine pattern present in animals with EAE. In particular, the role of the so-called Th1- and Th2-cytokines has been addressed. In a recent study, it has been demonstrated that IL-23 rather than IL-12 is critical for modulating the character of the developing immune response towards a proinflammatory response and leading to EAE. IL-17 is a crucial effector cytokine, whose production is specifically triggered by IL-23, and it has been shown to be an essential inflammatory mediator in other autoimmune diseases and inflammatory conditions. This led us to investigate the role of IL-17 in EAE. Strong antigen-specific production of IL-17 was demonstrated both in peripheral immune organs and in the CNS in acute and chronic EAE, as demonstrated by ELISPOT and RT-PCR analysis. Therapeutic neutralization of IL-17 with IL-17-receptor-Fc-protein in acute EAE ameliorated clinical symptoms. Neutralization of IL-17 with a monoclonal antibody also ameliorated the disease course. We conclude that IL-17 is crucially involved in the cytokine network as an effector cytokine in EAE.

    Original languageEnglish
    JournalCellular Immunology
    Volume237
    Issue number2
    Pages (from-to)123-130
    Number of pages8
    ISSN0008-8749
    DOIs
    Publication statusPublished - 10.2005

    Research Areas and Centers

    • Academic Focus: Center for Infection and Inflammation Research (ZIEL)

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