Therapeutic efficacy of IL-17 neutralization in murine experimental autoimmune encephalomyelitis.
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.
Hofstetter
Harald H
HH
Clinical Research Group for Multiple Sclerosis, Department of Neurology, University of Würzburg, Würzburg, Germany.
Ibrahim
Saleh M
SM
Koczan
Dirk
D
Kruse
Niels
N
Weishaupt
Andreas
A
Toyka
Klaus V
KV
Gold
Ralf
R
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage; D001483:Base Sequence; D018076:DNA, Complementary / Q000235:genetics; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology* / Q000628:therapy*; D006023:Glycoproteins / Q000276:immunology; D006801:Humans; D020381:Interleukin-17 / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000235:genetics; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D009500:Neutralization Tests; D010446:Peptide Fragments / Q000276:immunology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D000911:Antibodies, Monoclonal; D018076:DNA, Complementary; D006023:Glycoproteins; C508840:IL23A protein, human; C508841:Il23a protein, mouse; D020381:Interleukin-17; D053759:Interleukin-23; D053760:Interleukin-23 Subunit p19; D007378:Interleukins; D063308:Myelin-Oligodendrocyte Glycoprotein; D010446:Peptide Fragments; D012333:RNA, Messenger; C445081:myelin oligodendrocyte glycoprotein (35-55)