title: Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
abstract: Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system with many similarities to multiple sclerosis. The main effector cells involved are CD4+ T cells, recognizing encephalitogenic epitopes within the central nervous system, and macrophages, both of which secrete proinflammatory cytokines, such as IFN-gamma and TNF. Studies have shown that immunomodulation of this inflammatory response by anti-inflammatory cytokines (IL-4, IL-10, IFN-beta, and TGF-beta) can reduce clinical severity in EAE. The importance of TNF in EAE has been demonstrated by using soluble TNF-receptor molecules to inhibit EAE. However, the limitation of this type of therapy is the necessity for frequent administration of cytokine proteins due to their short biologic half-life. This study demonstrates that EAE can be inhibited by a single injection of therapeutic cytokine (IL-4, IFN-beta, and TGF-beta) DNA-cationic liposome complex directly into the central nervous system. DNA coding for a novel, dimeric form of human p75 TNF receptor also ameliorated clinical EAE. Local administration of DNA-cationic liposome complex has identified gene targets that may be more efficiently exploited using vectors producing more stable expression for effective treatment of neuroimmunologic disease.
authors.affiliation: Department of Clinical Ophthalmology, Institute of Ophthalmology, University College London, United Kingdom. jcroxfor@hgmp.mrc.ac.uk
authors.forename: J L
authors.initials: JL
authors.lastname: Croxford
authors.forename: K
authors.initials: K
authors.lastname: Triantaphyllopoulos
authors.forename: O L
authors.initials: OL
authors.lastname: Podhajcer
authors.forename: M
authors.initials: M
authors.lastname: Feldmann
authors.forename: D
authors.initials: D
authors.lastname: Baker
authors.forename: Y
authors.initials: Y
authors.lastname: Chernajovsky
mesh_terms: D000818:Animals; D001921:Brain / Q000378:metabolism; D016207:Cytokines / Q000032:analysis / Q000235:genetics*; D004247:DNA / Q000008:administration & dosage*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000517:prevention & control*; D015316:Genetic Therapy; D007150:Immunohistochemistry; D016899:Interferon-beta / Q000235:genetics; D008081:Liposomes; D008297:Male; D051379:Mice; D010957:Plasmids
chemical_list: D016207:Cytokines; D008081:Liposomes; D016899:Interferon-beta; D004247:DNA