Arvanil inhibits T lymphocyte activation and ameliorates autoimmune encephalomyelitis.
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.
Malfitano
Anna Maria
AM
Dipartimento di Scienze Farmaceutiche, Universita' di Salerno, Via Ponte don Melillo 84084 Fisciano (Salerno), Italy.
Matarese
Giuseppe
G
Pisanti
Simona
S
Grimaldi
Claudia
C
Laezza
Chiara
C
Bisogno
Tiziana
T
Di Marzo
Vincenzo
V
Lechler
Robert I
RI
Bifulco
Maurizio
M
D000818:Animals; D001095:Arachidonic Acids / Q000494:pharmacology; D015153:Blotting, Western / Q000379:methods; D001835:Body Weight / Q000187:drug effects; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects; D063385:Cannabinoid Receptor Modulators / Q000494:pharmacology; D002211:Capsaicin / Q000819:agonists / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004306:Dose-Response Relationship, Immunologic; D004347:Drug Interactions; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology; D063388:Endocannabinoids; D004789:Enzyme Activation / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry / Q000379:methods; D006801:Humans; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D008213:Lymphocyte Activation / Q000187:drug effects*; D051379:Mice; D018991:Myelin Proteolipid Protein / Q000008:administration & dosage; D010446:Peptide Fragments / Q000008:administration & dosage; D053284:Polyunsaturated Alkamides; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D018709:Statistics, Nonparametric; D013997:Time Factors
D001095:Arachidonic Acids; D063385:Cannabinoid Receptor Modulators; D016207:Cytokines; D063388:Endocannabinoids; D018991:Myelin Proteolipid Protein; D010446:Peptide Fragments; D053284:Polyunsaturated Alkamides; C121153:arvanil; C435023:myelin proteolipid protein (139-151); D051057:Proto-Oncogene Proteins c-akt; D002211:Capsaicin; C078814:anandamide