Jl. Croxford et al., CYTOKINE GENE-THERAPY IN EXPERIMENTAL ALLERGIC ENCEPHALOMYELITIS BY INJECTION OF PLASMID DNA CATIONIC LIPOSOME COMPLEX INTO THE CENTRAL-NERVOUS-SYSTEM, The Journal of immunology, 160(10), 1998, pp. 5181-5187
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.