Details

Autor(en) / Beteiligte

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

Titel

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

Ist Teil von

• Cellular Immunology, 2005-10, Vol.237 (2), p.123-130

Ort / Verlag

Netherlands: Elsevier Inc

Erscheinungsjahr

2005

Quelle

Elsevier ScienceDirect Journals

Beschreibungen/Notizen

• 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.