Effect of IL-12 encoding plasmid administration on tight-skin mouse

The tight-skin (Tsk/+) mutant mice, a putative murine model of scleroderma, are characterized by the excessive deposition of collagen and the presence of antinuclear antibodies. Type 2 cytokines, such as IL-4 and IL-6, are ca pable of regulating the synthesis of various matrix molecules, including ty pe I collagen, by fibroblasts. IL-12 is well known to induce type 1 cytokin e production and to reduce type 2 activity. Here, we examined the effect of IL-12 encoding plasmid (pCAGGSIL-12) on the disease progression of Tsk/+ m ice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscul arly 7 times at 3 week. intervals into Tsk/+ mice. One week after the last injection, pCAGGSIL-12 administered Tsk/+ mice exhibited a marked decrease in the skin thickness compared with the mice treated with pCAGGS vector. Th e serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 tre ated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These res ults indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficia l effects in preventing the collagen accumulation in the skin and suppressi ng the autoimmunity via improvement of Th1/Th2 balance. The present study s uggests that the IL-12 encoding plasmid administration might have a therape utic effect on systemic sclerosis. (C) 2001 Academic Press.