title: Characterization of relapsing autoimmune encephalomyelitis and its treatment with decoy chemokine receptor genes.
abstract: To elucidate the pathomechanisms of relapses of autoimmune disorders and to develop immunotherapy against relapses, we induced acute monophasic and chronic relapsing (CR) experimental autoimmune encephalomyelitis (EAE) in DA rats. Immunopathological and cytokine-chemokine analyses demonstrated that the number of infiltrating macrophages was significantly elevated in the CR-EAE than in acute EAE lesions and that IFN-gamma and IP-10 in the spinal cord were significantly upregulated during the first attack and relapse of CR-EAE, respectively, than at the peak of acute EAE. In vivo administration of decoy chemokine receptor plasmid DNAs encoding the binding sites of CXCR3 and CCR2 suppressed the development of relapse of CR-EAE. Importantly, multiple injections of DNAs did not elicit the antibody production against chemokine receptors. Taken together, these findings demonstrated that neutralization therapy with decoy chemokine receptor DNAs is effective to control autoimmune diseases.
authors.affiliation: Department of Molecular Neuropathology, Tokyo Metropolitan Institute for Neuroscience, Musashidai 2-6, Fuchu, Tokyo 183-8526, Japan. matyoh@tmin.ac.jp
authors.forename: Yoh
authors.initials: Y
authors.lastname: Matsumo
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sakuma
authors.forename: Akira
authors.initials: A
authors.lastname: Miyakoshi
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Tsukada
authors.forename: Kuniko
authors.initials: K
authors.lastname: Kohyama
authors.forename: Il-Kwon
authors.initials: IK
authors.lastname: Park
authors.forename: Naoyuki
authors.initials: N
authors.lastname: Tanuma
mesh_terms: D000208:Acute Disease; D000818:Animals; D000941:Antigens / Q000502:physiology; D002465:Cell Movement; D049109:Cell Proliferation; D002490:Central Nervous System / Q000473:pathology; D018925:Chemokines / Q000235:genetics / Q000378:metabolism; D002908:Chronic Disease; D016207:Cytokines / Q000378:metabolism; D004247:DNA / Q000627:therapeutic use; D015536:Down-Regulation; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000276:immunology / Q000473:pathology* / Q000503:physiopathology* / Q000628:therapy; D015316:Genetic Therapy; D007114:Immunization; D007167:Immunotherapy; D008264:Macrophages / Q000473:pathology; D004676:Myelin Basic Protein / Q000276:immunology; D009185:Myelin Proteins; D009186:Myelin Sheath / Q000276:immunology; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D019707:Receptors, Chemokine / Q000235:genetics*; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology / Q000473:pathology
chemical_list: D000941:Antigens; D018925:Chemokines; D016207:Cytokines; C571328:Mog protein, rat; D004676:Myelin Basic Protein; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger; D019707:Receptors, Chemokine; D004247:DNA