Anti-encephalitogenic effects of ethyl pyruvate are reflected in the central nervous system and the gut

Biomed Pharmacother. 2017 Dec;96:78-85. doi: 10.1016/j.biopha.2017.09.110. Epub 2017 Sep 28.

Abstract

Ethyl pyruvate is a redox analogue of dimethyl fumarate (Tecfidera), a drug for multiple sclerosis treatment. We have recently shown that ethyl pyruvate ameliorates experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis. It affects encephalitogenic T cells and macrophages in vitro, as well as in lymph nodes draining the site of encephalitogenic immunization and within the central nervous system (CNS). Here, in vivo effects of ethyl pyruvate on EAE are thoroughly investigated in the CNS and within the gut associated lymphoid tissue. Ethyl pyruvate reduced infiltrates within the CNS and number of activated macrophages/microglia (ED1+/Iba1+) and proliferating astrocytes (GFAP+). Furthermore, it reduced expression of HMGB1 in activated macrophages/microglia. It also reduced number of activated T cells and antigen-presenting cells and expression of Th1/Th17-related molecules in mesenteric lymph nodes and Peyer's patches. These results contribute to our understanding of anti-encephalitogenic effects of ethyl pyruvate as they provide evidence of its effects within the CNS and imply that these effects are related to reduction of inflammatory immune response in gut associated lymphoid tissue.

Keywords: HMGB1; ethyl pyruvate; experimental autoimmune encephalomyelitis; gut associated lymphoid tissue; multiple sclerosis.

MeSH terms

  • Animals
  • Central Nervous System / drug effects*
  • Central Nervous System / metabolism
  • Central Nervous System / pathology
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / metabolism
  • Encephalomyelitis, Autoimmune, Experimental / pathology
  • Female
  • Gastrointestinal Tract / drug effects*
  • Gastrointestinal Tract / metabolism
  • Gastrointestinal Tract / pathology
  • HMGB1 Protein / antagonists & inhibitors
  • HMGB1 Protein / biosynthesis
  • Lymph Nodes / drug effects
  • Lymph Nodes / metabolism
  • Lymph Nodes / pathology
  • Peyer's Patches / drug effects
  • Peyer's Patches / metabolism
  • Peyer's Patches / pathology
  • Pyruvates / pharmacology
  • Pyruvates / therapeutic use*
  • Rats
  • Treatment Outcome

Substances

  • HMGB1 Protein
  • Hbp1 protein, rat
  • Pyruvates
  • ethyl pyruvate