Downregulation of IL-17 and IL-6 in the central nervous system by glatiramer acetate in experimental autoimmune encephalomyelitis

J Neuroimmunol. 2008 Nov 15;204(1-2):58-65. doi: 10.1016/j.jneuroim.2008.07.018.

Abstract

T helper 17 (Th17) cells are pivotal in the immune pathogenesis of EAE. Glatiramer acetate (GA) can enhance Treg FOXp3 expression. We demonstrate that GA downregulates the expression of both IL-17 and IL-6 in two different EAE models. Increased mRNA expression in CNS for ROR gamma t, IL-17, IL-12/IL-23, IL-6, TNF-alpha, STAT4 and Th1 cytokines were significantly reduced by GA with a concomitant rise in SMAD3. The increased expression of TNF-alpha, IL-6, and IL-17 in CNS of CD25+ depleted animals was suppressed by GA treatment. This study demonstrates that both Th1 polarization and Th17 expression are modulated by GA.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • CD4-Positive T-Lymphocytes / pathology
  • Central Nervous System / drug effects*
  • Cytokines / metabolism
  • Disease Models, Animal
  • Down-Regulation / drug effects*
  • Down-Regulation / genetics
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / genetics
  • Encephalomyelitis, Autoimmune, Experimental / pathology*
  • Encephalomyelitis, Autoimmune, Experimental / prevention & control
  • Female
  • Forkhead Transcription Factors / metabolism
  • Glatiramer Acetate
  • Glycoproteins
  • Immunosuppressive Agents / pharmacology*
  • Immunosuppressive Agents / therapeutic use
  • Interleukin-17 / genetics
  • Interleukin-17 / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • Mice
  • Mice, Inbred C57BL
  • Mice, Transgenic
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Peptides / pharmacology*
  • Peptides / therapeutic use
  • RNA, Messenger / metabolism
  • Receptors, Antigen, T-Cell / genetics
  • STAT4 Transcription Factor / metabolism
  • Smad3 Protein / metabolism

Substances

  • Cytokines
  • Forkhead Transcription Factors
  • Foxp3 protein, mouse
  • Glycoproteins
  • Immunosuppressive Agents
  • Interleukin-17
  • Interleukin-6
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Peptides
  • RNA, Messenger
  • Receptors, Antigen, T-Cell
  • STAT4 Transcription Factor
  • Smad3 Protein
  • Smad3 protein, mouse
  • Stat4 protein, mouse
  • myelin oligodendrocyte glycoprotein (35-55)
  • Glatiramer Acetate