Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis

J Neuroimmunol. 2006 Feb;171(1-2):110-9. doi: 10.1016/j.jneuroim.2005.09.005. Epub 2005 Oct 18.

Abstract

This study examined the immunomodulatory effect of arvanil, a synthetic capsaicin-anandamide hybrid. Arvanil inhibits lymphocyte proliferation and IFN-gamma production. The phenotype of activated CD4+T cells treated with arvanil shows a down-regulation of T cell activation markers such as CD25, HLA-DR and CD134/OX40. Arvanil and anandamide do not induce apoptosis on CD4+T cells. Arvanil blocks the G1/S phase transition of the cell cycle in stimulated peripheral blood mononuclear cells, inducing activation of p21waf-1/cip-1 and phosphorylation of Akt/PKB. In vivo, arvanil ameliorates experimental autoimmune encephalomyelitis in the SJL/J mouse. Our findings have relevance for the use of arvanil and related compounds as a novel immunotherapeutic approach in the treatment of multiple sclerosis.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arachidonic Acids / pharmacology
  • Blotting, Western / methods
  • Body Weight / drug effects
  • CD4-Positive T-Lymphocytes / drug effects
  • Cannabinoid Receptor Modulators / pharmacology
  • Capsaicin / agonists
  • Capsaicin / analogs & derivatives*
  • Capsaicin / chemistry
  • Capsaicin / pharmacology
  • Capsaicin / therapeutic use
  • Cell Line
  • Cell Proliferation / drug effects
  • Cytokines / metabolism
  • Disease Models, Animal
  • Dose-Response Relationship, Drug
  • Dose-Response Relationship, Immunologic
  • Drug Interactions
  • Encephalomyelitis, Autoimmune, Experimental / chemically induced
  • Encephalomyelitis, Autoimmune, Experimental / drug therapy*
  • Encephalomyelitis, Autoimmune, Experimental / immunology
  • Endocannabinoids
  • Enzyme Activation / drug effects
  • Female
  • Flow Cytometry / methods
  • Humans
  • Leukocytes, Mononuclear / drug effects
  • Lymphocyte Activation / drug effects*
  • Mice
  • Myelin Proteolipid Protein / administration & dosage
  • Peptide Fragments / administration & dosage
  • Polyunsaturated Alkamides
  • Proto-Oncogene Proteins c-akt / metabolism
  • Statistics, Nonparametric
  • Time Factors

Substances

  • Arachidonic Acids
  • Cannabinoid Receptor Modulators
  • Cytokines
  • Endocannabinoids
  • Myelin Proteolipid Protein
  • Peptide Fragments
  • Polyunsaturated Alkamides
  • arvanil
  • myelin proteolipid protein (139-151)
  • Proto-Oncogene Proteins c-akt
  • Capsaicin
  • anandamide