Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis.

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.

• Authors: Anna Maria Malfitano, Giuseppe Matarese, Simona Pisanti, Claudia Grimaldi, Chiara Laezza, Tiziana Bisogno, Vincenzo Di Marzo, Robert I Lechler, Maurizio Bifulco
• Journal: Journal of neuroimmunology (J Neuroimmunol) Vol. 171 Issue 1-2 Pg. 110-9 (Feb 2006) ISSN: 0165-5728 [Print] Netherlands
• PMID: 16239036 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• 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

Topics

• Animals
• Arachidonic Acids (pharmacology)
• Blotting, Western (methods)
• Body Weight (drug effects)
• CD4-Positive T-Lymphocytes (drug effects)
• Cannabinoid Receptor Modulators (pharmacology)
• Capsaicin (agonists, analogs & derivatives, chemistry, pharmacology, 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, drug therapy, 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