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
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Comparative Study
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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Arachidonic Acids / pharmacology
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Blotting, Western / methods
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Body Weight / drug effects
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CD4-Positive T-Lymphocytes / drug effects
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Cannabinoid Receptor Modulators / pharmacology
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Capsaicin / agonists
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Capsaicin / analogs & derivatives*
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Capsaicin / chemistry
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Capsaicin / pharmacology
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Capsaicin / therapeutic use
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Cell Line
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Cell Proliferation / drug effects
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Cytokines / metabolism
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Disease Models, Animal
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Dose-Response Relationship, Drug
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Dose-Response Relationship, Immunologic
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Drug Interactions
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Encephalomyelitis, Autoimmune, Experimental / chemically induced
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Encephalomyelitis, Autoimmune, Experimental / drug therapy*
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Encephalomyelitis, Autoimmune, Experimental / immunology
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Endocannabinoids
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Enzyme Activation / drug effects
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Female
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Flow Cytometry / methods
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Humans
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Leukocytes, Mononuclear / drug effects
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Lymphocyte Activation / drug effects*
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Mice
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Myelin Proteolipid Protein / administration & dosage
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Peptide Fragments / administration & dosage
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Polyunsaturated Alkamides
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Proto-Oncogene Proteins c-akt / metabolism
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Statistics, Nonparametric
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Time Factors
Substances
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Arachidonic Acids
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Cannabinoid Receptor Modulators
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Cytokines
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Endocannabinoids
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Myelin Proteolipid Protein
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Peptide Fragments
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Polyunsaturated Alkamides
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arvanil
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myelin proteolipid protein (139-151)
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Proto-Oncogene Proteins c-akt
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Capsaicin
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anandamide