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.