Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery

Details

Serval ID
serval:BIB_B6938D3129D5
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Modulation of disease activity in murine systemic lupus erythematosus by cytokine gene delivery
Journal
Lupus
Author(s)
Raz  E., Dudler  J., Lotz  M., Baird  S. M., Berry  C. C., Eisenberg  R. A., Carson  D. A.
ISSN
0961-2033 (Print)
Publication state
Published
Issued date
08/1995
Volume
4
Number
4
Pages
286-92
Notes
Comparative Study
Journal Article
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, P.H.S. --- Old month value: Aug
Abstract
Somatic gene therapy is a novel approach with the potential to achieve prolonged increases in circulating levels of peptide hormones and cytokines. The present study evaluates the effects of monthly, intramuscular injections of cDNA expression vectors encoding for transforming growth factor beta (TGF beta) or interleukin 2 (IL-2) on disease activity in the MRL/lpr/lpr murine model of systemic lupus erythematosus (SLE). Monthly injections of plasmids cDNA between 6 and 26 weeks significantly elevated the serum levels of TGF beta (P < 0.005) and IL-2 (P < 0.05) compared with a control plasmid without insert. TGF beta encoding plasmid had beneficial effects in murine SLE with a prolonged survival of 70% at 26 weeks compared with 40% in the control group, decreased anti-chromatin and rheumatoid factor antibodies and a 50% decrease in total IgG production. Renal function was improved with reduced BUN levels and kidney inflammation as estimated by an histologic score. Those beneficial effects occurred in the apparent absence of local or systemic side-effects. In contrast, IL-2 cDNA injections appeared harmful with a decreased survival to 20% at 26 weeks, enhanced total IgG synthesis and autoantibodies production with a 4.5-fold increase in antichromatin antibodies. These results indicate that somatic gene therapy may provide a simple, inexpensive and effective mechanism for the long-term control of autoimmune diseases.
Keywords
Animals Autoantibodies/biosynthesis/drug effects DNA, Complementary/*administration & dosage/therapeutic use Disease Models, Animal *Gene Therapy Immunoglobulin G/biosynthesis/drug effects Injections, Intramuscular Interleukin-2/*blood Lupus Erythematosus, Systemic/blood/*drug therapy/pathology Lymphotoxin-alpha/*blood Male Mice Random Allocation Survival Rate
Pubmed
Web of science
Create date
25/01/2008 8:32
Last modification date
20/08/2019 15:24
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