title: Opioid growth factor suppresses expression of experimental autoimmune encephalomyelitis.
abstract: Naltrexone, an opioid antagonist, has been shown to modulate expression of experimental autoimmune encephalomyelitis (EAE), an animal model of MS, suggesting that endogenous opioids are inhibitory trophic factors in EAE. In the present study, we investigated the effects of one native opioid peptide, opioid growth factor ([Met(5)]-enkephalin), on the onset and progression of EAE. C57Bl/6 mice injected with myelin oligodendrocyte glycoprotein (MOG) received daily injections of 10 mg/kg OGF (MOG+OGF) or saline (MOG+Vehicle). Over 60% of the MOG+OGF animals did not exhibit behavioral signs of disease (EAE) in contrast to 100% of the mice in the MOG+Vehicle group. The severity and disease indices of EAE in the OGF-treated mice were markedly reduced from MOG+Vehicle cohorts. By day 30, 60% of MOG+OGF mice had a remission, relative to 4% in the MOG+Vehicle group. MOG-injected mice receiving OGF had significant reductions in activated astrocytes and damaged neurons compared to MOG+Vehicle animals. Unlike MOG+Vehicle and MOG+OGF mice with behavioral signs of disease, MOG+OGF animals without manifestation of disease had no lumbar spinal cord demyelination. Both OGF and OGF receptor were detected in splenic-derived T lymphocytes by immunohistochemistry. OGF treatment decreased both DNA synthesis and cell proliferation in comparison to vehicle-treated T cell lymphocyte cultures. These results indicate that an endogenous opioid, OGF, inhibits the onset and progression of EAE, and suggest that clinical studies on the use of OGF treatment for MS are merited.
authors.affiliation: Department of Neural and Behavioral Sciences, The Pennsylvania State University College of Medicine, Hershey, PA, USA. isz1@psu.edu
authors.forename: Ian S
authors.initials: IS
authors.lastname: Zagon
authors.forename: Kristen A
authors.initials: KA
authors.lastname: Rahn
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bonneau
authors.forename: Anthony P
authors.initials: AP
authors.lastname: Turel
authors.forename: Patricia J
authors.initials: PJ
authors.lastname: McLaughlin
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D018450:Disease Progression; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D004744:Enkephalin, Methionine / Q000378:metabolism / Q000627:therapeutic use*; D005260:Female; D006023:Glycoproteins; D008213:Lymphocyte Activation / Q000276:immunology; D051379:Mice; D008810:Mice, Inbred C57BL; D063308:Myelin-Oligodendrocyte Glycoprotein; D018377:Neurotransmitter Agents / Q000627:therapeutic use*; D010446:Peptide Fragments; D011957:Receptors, Opioid / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000473:pathology; D013997:Time Factors
chemical_list: D006023:Glycoproteins; D063308:Myelin-Oligodendrocyte Glycoprotein; D018377:Neurotransmitter Agents; D010446:Peptide Fragments; D011957:Receptors, Opioid; C033593:methionine-enkephalin receptor; C445081:myelin oligodendrocyte glycoprotein (35-55); D004744:Enkephalin, Methionine