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IL-12-ENCODING PLASMID HAS A BENEFICIAL EFFECT ON SPONTANEOUS AUTOIMMUNE DISEASE IN MRL/MP-lpr/lpr MICE

Authors
Publisher
Elsevier Ltd
Publication Date
Volume
12
Issue
7
Identifiers
DOI: 10.1006/cyto.1999.0662
Keywords
  • Autoimmunity/Gene Therapy/Il-12/Lupus/Th1/Th2
Disciplines
  • Biology
  • Medicine

Abstract

Abstract Systemic lupus erythematosus (SLE) is characterized by immune abnormalities explained by the overproduction of Th 2cytokines such as autoantibody production and polyclonal B cell activation. We examined the effect of administering a DNA plasmid encoding IL-12 on the lupus-like disease of MRL/MP-lpr/lpr (MRL/lpr) mice. Treatments were delivered intramuscularly every 4 weeks, starting at 4 weeks of age. This intervention significantly inhibited the accumulation of CD4 −CD8 −T cells, and reduced lymphadenopathy and splenomegaly. A significant decrease in serum IgG anti-DNA autoantibody titers was observed, and plasmid IL-12 therapy was also associated with a reduction in the proteinuria and glomerulonephritis characteristic of this disease. Serum IFN-γ level was increased by inoculating IL-12 encoding plasmid, suggesting that the cytokine balance was skewed towards Th 1. The clinical implications of this suppression of autoimmune disease are also discussed.

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