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 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-gamma 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.
Hagiwara
E
E
Department of Internal Medicine, Yokohama City University of Medical School, Yokohama, Japan. hagiwara@med.yokohama-cu.ac.jp
Okubo
T
T
Aoki
I
I
Ohno
S
S
Tsuji
T
T
Ihata
A
A
Ueda
A
A
Shirai
A
A
Okuda
K
K
Miyazaki
J
J
Ishigatsubo
Y
Y
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D015316:Genetic Therapy / Q000379:methods; D005921:Glomerulonephritis / Q000097:blood / Q000276:immunology / Q000628:therapy; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000235:genetics* / Q000276:immunology / Q000627:therapeutic use; D008180:Lupus Erythematosus, Systemic / Q000097:blood / Q000276:immunology / Q000628:therapy*; D008206:Lymphatic Diseases / Q000097:blood / Q000276:immunology / Q000628:therapy; D051379:Mice; D019463:Mice, Inbred MRL lpr; D010957:Plasmids
D000974:Antibodies, Antinuclear; D018664:Interleukin-12; D007371:Interferon-gamma