IL-12-encoding plasmid has a beneficial, effect on spontaneous autoimmune disease in MRL/MP-lpr/lpr mice

Systemic lupus erythematosus (SLE) is characterized by immune abnormalities explained by the overproduction of Th-2 cytokines such as autoantibody pro duction and polyclonal B cell activation. We examined the effect of adminis tering 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 week s, starting at 4 weeks of age. This intervention significantly inhibited th e accumulation of CD4(-) CD8(-) T cells, and reduced lymphadenopathy and sp lenomegaly, A significant decrease in serum IgG anti-DNA autoantibody titer s was observed, and plasmid IL-12 therapy was also associated with a reduct ion in the proteinuria and glomerulonephritis characteristic of this diseas e, Serum IFN-gamma level was increased by inoculating IL-12 encoding plasmi d, suggesting that the cytokine balance was skewed towards Th-1, The clinic al implications of this suppression of autoimmune disease are also discusse d. (C) 2000 Academic Press.