Decitabine induces regulatory T cells, inhibits the production of IFN-gamma and IL-17 and exerts preventive and therapeutic efficacy in rodent experimental autoimmune neuritis

J Neuroimmunol. 2018 Aug 15:321:41-48. doi: 10.1016/j.jneuroim.2018.05.013. Epub 2018 May 28.

Abstract

Guillain-Barré syndrome (GBS) is an immune-mediated acute disorder of the peripheral nervous system. Despite treatment, there is an associated mortality and severe disability in 9 to 17% of the cases. Decitabine (DAC) is a hypomethylating drug used in myelodisplastic syndrome, that has been shown to exert immunomodulatory effects. We have evaluated the effects of DAC in two rodent models of GBS, the Experimental Allergic Neuritis (EAN). Both prophylactic and therapeutic treatment with DAC ameliorated the clinical course of EAN, increasing the numbers of thymic regulatory T cells and reducing the production of proinflammmatory cytokines. Our data suggest the possible use of decitabine for the treatment of GBS.

Keywords: Decitabine; Experimental allergic neuritis; Guillain Barrè syndrome; Regulatory T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Decitabine / pharmacology*
  • Enzyme Inhibitors / pharmacology*
  • Interferon-gamma / biosynthesis
  • Interferon-gamma / drug effects
  • Interleukin-17 / biosynthesis
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Neuritis, Autoimmune, Experimental / immunology
  • Neuritis, Autoimmune, Experimental / pathology*
  • Rats
  • Rats, Inbred Lew
  • T-Lymphocytes, Regulatory / drug effects*
  • T-Lymphocytes, Regulatory / immunology

Substances

  • Enzyme Inhibitors
  • Interleukin-17
  • Decitabine
  • Interferon-gamma