Dimethyl fumarate: Regulatory effects on the immune system in the treatment of multiple sclerosis

J Cell Physiol. 2019 Jul;234(7):9943-9955. doi: 10.1002/jcp.27930. Epub 2018 Dec 7.

Abstract

Dimethyl fumarate (DMF) is an important oral treatment option for various autoimmune diseases, such as multiple sclerosis (MS) and psoriasis. DMF and its dynamic metabolite, monomethyl fumarate (MMF) are the major compounds that exert therapeutic effects on several pathologic conditions in part, through downregulation of immune responses. The exact mechanism of DMF is yet to be fully understood even though its beneficial effects on the immune system are extensively studied. It has been shown that DMF/MMF can affect various immune cells, which can get involved in both the naive and adaptive immune systems, such as T cells, B cells, dendritic cells, macrophages, neutrophils, and natural killer cells. It is suggested that DMF/MMF may exert their effect on immune cells through inhibition of nuclear factor-κB translocation, upregulation of nuclear factor erythroid-derived 2(E2)-related factor antioxidant pathway, and activation of hydroxyl carboxylic acid receptor 2. In this review, the mechanisms underlying the modulatory functions of DMF or MMF on the main immune cell populations involved in the immunopathogenesis of MS are discussed.

Keywords: dimethyl fumarate; immune system; multiple sclerosis; treatment.

Publication types

  • Review

MeSH terms

  • Adaptive Immunity / drug effects*
  • Animals
  • Dimethyl Fumarate / adverse effects
  • Dimethyl Fumarate / pharmacokinetics
  • Dimethyl Fumarate / therapeutic use*
  • Humans
  • Immune System / drug effects*
  • Immune System / immunology
  • Immune System / physiopathology
  • Immunity, Innate / drug effects*
  • Immunosuppressive Agents / adverse effects
  • Immunosuppressive Agents / pharmacokinetics
  • Immunosuppressive Agents / therapeutic use*
  • Multiple Sclerosis / diagnosis
  • Multiple Sclerosis / drug therapy*
  • Multiple Sclerosis / immunology
  • Multiple Sclerosis / physiopathology
  • Signal Transduction

Substances

  • Immunosuppressive Agents
  • Dimethyl Fumarate