CYTOKINE GENE-THERAPY IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY INJECTION OF PLASMID DNA CATIONIC LIPOSOME COMPLEX INTO THE CENTRAL-NERVOUS-SYSTEM

Experimental allergic encephalomyelitis (EAE) is an autoimmune disease of the central nervous system with many similarities to multiple scle rosis, The main effector cells involved are CD4(+) T cells, recognizin g encephalitogenic epitopes within the central nervous system, and mac rophages, both of which secrete proinflammatory cytokines, such as IFN -gamma and TNF, Studies have shown that immunomodulation of this infla mmatory 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 molecu les 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 ce ntral nervous system. DNA coding for a novel, dimeric form of human p7 5 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 express ion for effective treatment of neuroimmunologic disease.