TY - JOUR
T1 - Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis
AU - Hofstetter, Harald H.
AU - Ibrahim, Saleh M.
AU - Koczan, Dirk
AU - Kruse, Niels
AU - Weishaupt, Andreas
AU - Toyka, Klaus V.
AU - Gold, Ralf
N1 - Funding Information:
We thank Gabi Köllner and R. Waterstraat for excellent technical assistance, and Helga Brünner and Dr. Bettina Holtmann for excellent animal care. The work was supported by a grant from the German Federal Ministry of Education and Research (BMBF) programme NBL3, 01 ZZ0108, to S.M.I.
PY - 2005/10
Y1 - 2005/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=30944452780&partnerID=8YFLogxK
U2 - 10.1016/j.cellimm.2005.11.002
DO - 10.1016/j.cellimm.2005.11.002
M3 - Journal articles
C2 - 16386239
AN - SCOPUS:30944452780
SN - 0008-8749
VL - 237
SP - 123
EP - 130
JO - Cellular Immunology
JF - Cellular Immunology
IS - 2
ER -
