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

Cell Immunol. 2005 Oct;237(2):123-30. doi: 10.1016/j.cellimm.2005.11.002. Epub 2005 Dec 28.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Monoclonal / administration & dosage
  • Base Sequence
  • DNA, Complementary / genetics
  • Encephalomyelitis, Autoimmune, Experimental / immunology*
  • Encephalomyelitis, Autoimmune, Experimental / therapy*
  • Glycoproteins / immunology
  • Humans
  • Interleukin-17 / antagonists & inhibitors*
  • Interleukin-17 / biosynthesis
  • Interleukin-17 / genetics
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Myelin-Oligodendrocyte Glycoprotein
  • Neutralization Tests
  • Peptide Fragments / immunology
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism

Substances

  • Antibodies, Monoclonal
  • DNA, Complementary
  • Glycoproteins
  • IL23A protein, human
  • Il23a protein, mouse
  • Interleukin-17
  • Interleukin-23
  • Interleukin-23 Subunit p19
  • Interleukins
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • RNA, Messenger
  • myelin oligodendrocyte glycoprotein (35-55)