title: Continued administration of ciliary neurotrophic factor protects mice from inflammatory pathology in experimental autoimmune encephalomyelitis.
abstract: Multiple sclerosis is an inflammatory disease of the central nervous system that leads to loss of myelin and oligodendrocytes and damage to axons. We show that daily administration (days 8 to 24) of murine ciliary neurotrophic factor (CNTF), a neurotrophic factor that has been described as a survival and differentiation factor for neurons and oligodendrocytes, significantly ameliorates the clinical course of a mouse model of multiple sclerosis. In the acute phase of experimental autoimmune encephalomyelitis induced by myelin oligodendrocyte glycoprotein peptide 35-55, treatment with CNTF did not change the peripheral immune response but did reduce the number of perivascular infiltrates and T cells and the level of diffuse microglial activation in spinal cord. Blood brain barrier permeability was significantly reduced in CNTF-treated animals. Beneficial effects of CNTF did not persist after it was withdrawn. After cessation of CNTF treatment, inflammation and symptoms returned to control levels. However, slight but significantly higher numbers of oligodendrocytes, NG2-positive cells, axons, and neurons were observed in mice that had been treated with high concentrations of CNTF. Our results show that CNTF inhibits inflammation in the spinal cord, resulting in amelioration of the clinical course of experimental autoimmune encephalomyelitis during time of treatment.
authors.affiliation: Department of Neuropathology, University of Göttingen, Göttingen, Germany.
authors.forename: Tanja
authors.initials: T
authors.lastname: Kuhlmann
authors.forename: Leah
authors.initials: L
authors.lastname: Remington
authors.forename: Isabelle
authors.initials: I
authors.lastname: Cognet
authors.forename: Lyne
authors.initials: L
authors.lastname: Bourbonniere
authors.forename: Simone
authors.initials: S
authors.lastname: Zehntner
authors.forename: Florence
authors.initials: F
authors.lastname: Guilhot
authors.forename: Alexandra
authors.initials: A
authors.lastname: Herman
authors.forename: Angélique
authors.initials: A
authors.lastname: Guay-Giroux
authors.forename: Jack P
authors.initials: JP
authors.lastname: Antel
authors.forename: Trevor
authors.initials: T
authors.lastname: Owens
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Gauchat
mesh_terms: D000818:Animals; D001369:Axons / Q000187:drug effects; D001812:Blood-Brain Barrier / Q000187:drug effects / Q000276:immunology; D049109:Cell Proliferation / Q000187:drug effects; D020934:Ciliary Neurotrophic Factor / Q000008:administration & dosage* / Q000493:pharmacokinetics / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000235:genetics; D004195:Disease Models, Animal; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000139:chemically induced*; D007249:Inflammation / Q000473:pathology; D007274:Injections, Intraperitoneal; D051379:Mice; D008810:Mice, Inbred C57BL; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein / Q000276:immunology; D063308:Myelin-Oligodendrocyte Glycoprotein; D009836:Oligodendroglia / Q000166:cytology / Q000187:drug effects / Q000473:pathology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000276:immunology; D013601:T-Lymphocytes / Q000166:cytology / Q000187:drug effects / Q000276:immunology
chemical_list: D020934:Ciliary Neurotrophic Factor; D016207:Cytokines; C571327:Mog protein, mouse; D009185:Myelin Proteins; D018992:Myelin-Associated Glycoprotein; D063308:Myelin-Oligodendrocyte Glycoprotein; D012333:RNA, Messenger