PT - JOURNAL ARTICLE AU - Croxford, J. Ludovic AU - Triantaphyllopoulos, Kostas AU - Podhajcer, Osvaldo L. AU - Feldmann, Marc AU - Baker, David AU - Chernajovsky, Yuti TI - Cytokine Gene Therapy in Experimental Allergic Encephalomyelitis by Injection of Plasmid DNA-Cationic Liposome Complex into the Central Nervous System DP - 1998 May 15 TA - The Journal of Immunology PG - 5181--5187 VI - 160 IP - 10 4099 - http://www.jimmunol.org/content/160/10/5181.short 4100 - http://www.jimmunol.org/content/160/10/5181.full SO - J. Immunol.1998 May 15; 160 AB - 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-γ and TNF. Studies have shown that immunomodulation of this inflammatory response by anti-inflammatory cytokines (IL-4, IL-10, IFN-β, and TGF-β) 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-β, and TGF-β) 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.