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 sclerosis. The main effector cells involved are CD4+ T cells, recognizing encephalitogenic epitopes within the central nervous system, and macrophages, both of whic...

Full description

Bibliographic Details
Main Authors: Croxford, J, Triantaphyllopoulos, K, Podhajcer, O, Feldmann, M, Baker, D, Chernajovsky, Y
Format: Journal article
Language:English
Published: 1998
_version_ 1826296306883100672
author Croxford, J
Triantaphyllopoulos, K
Podhajcer, O
Feldmann, M
Baker, D
Chernajovsky, Y
author_facet Croxford, J
Triantaphyllopoulos, K
Podhajcer, O
Feldmann, M
Baker, D
Chernajovsky, Y
author_sort Croxford, J
collection OXFORD
description 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.
first_indexed 2024-03-07T04:14:19Z
format Journal article
id oxford-uuid:c8e59fe2-4094-46c8-81eb-b2f847ff133b
institution University of Oxford
language English
last_indexed 2024-03-07T04:14:19Z
publishDate 1998
record_format dspace
spelling oxford-uuid:c8e59fe2-4094-46c8-81eb-b2f847ff133b2022-03-27T06:55:12ZCytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:c8e59fe2-4094-46c8-81eb-b2f847ff133bEnglishSymplectic Elements at Oxford1998Croxford, JTriantaphyllopoulos, KPodhajcer, OFeldmann, MBaker, DChernajovsky, YExperimental 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.
spellingShingle Croxford, J
Triantaphyllopoulos, K
Podhajcer, O
Feldmann, M
Baker, D
Chernajovsky, Y
Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title_full Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title_fullStr Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title_full_unstemmed Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title_short Cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid DNA-cationic liposome complex into the central nervous system.
title_sort cytokine gene therapy in experimental allergic encephalomyelitis by injection of plasmid dna cationic liposome complex into the central nervous system
work_keys_str_mv AT croxfordj cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem
AT triantaphyllopoulosk cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem
AT podhajcero cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem
AT feldmannm cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem
AT bakerd cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem
AT chernajovskyy cytokinegenetherapyinexperimentalallergicencephalomyelitisbyinjectionofplasmiddnacationicliposomecomplexintothecentralnervoussystem