Treatment of murine lupus with cDNA encoding IFN-gammaR/Fc.
J Clin Invest
; 106(2): 207-15, 2000 Jul.
Article
em En
| MEDLINE
| ID: mdl-10903336
ABSTRACT
IFN-gamma, a pleiotropic cytokine, is a key effector molecule in the pathogenesis of several autoimmune diseases, including lupus. Importantly, deletion of IFN-gamma or IFN-gammaR in several lupus-predisposed mouse strains resulted in significant disease reduction, suggesting the potential for therapeutic intervention. We evaluated whether intramuscular injections of plasmids with cDNA encoding IFN-gammaR/Fc can retard lupus development and progression in MRL-Fas(lpr) mice. Therapy significantly reduced serum levels of IFN-gamma, as well as disease manifestations (autoantibodies, lymphoid hyperplasia, glomerulonephritis, mortality), when treatment was initiated at the predisease stage, particularly when IFN-gammaR/Fc expression was enhanced by electroporation at the injection site. Remarkably, disease was arrested and even ameliorated when this treatment was initiated at an advanced stage. This therapy represents a rare example of disease reversal and makes application of this nonviral gene therapy in humans with lupus (and perhaps other autoimmune/inflammatory conditions) highly promising.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Fragmentos Fc das Imunoglobulinas
/
Receptores de Interferon
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DNA Complementar
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Lúpus Eritematoso Sistêmico
Limite:
Animals
Idioma:
En
Revista:
J Clin Invest
Ano de publicação:
2000
Tipo de documento:
Article
País de afiliação:
Estados Unidos