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 capable of regulating the synthesis of various matrix molecules, including type I collagen, by fibroblasts. IL-12 is well known to induce type 1 cytokine 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/+ mice. pCAGGSIL-12 plasmid or pCAGGS parental vector was injected intramuscularly 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. The serum levels of antinuclear antibodies were diminished in pCAGGSIL-12 treated mice. IL-4 production by spleen cells from pCAGGSIL-12 plasmid treated mice was significantly lower than that from vector treated mice. These results indicate that pCAGGSIL-12 administration into Tsk/+ mice had beneficial effects in preventing the collagen accumulation in the skin and suppressing the autoimmunity via improvement of Th1/Th2 balance. The present study suggests that the IL-12 encoding plasmid administration might have a therapeutic effect on systemic sclerosis.
Tsuji-Yamada
J
J
Department of Dermatology, Yokohama City University, School of Medicine, Yokohama, Japan.
Nakazawa
M
M
Takahashi
K
K
Iijima
K
K
Hattori
S
S
Okuda
K
K
Minami
M
M
Ikezawa
Z
Z
Sasaki
T
T
D000818:Animals; D000974:Antibodies, Antinuclear / Q000097:blood; D015316:Genetic Therapy; D007273:Injections, Intramuscular; D007371:Interferon-gamma / Q000097:blood; D018664:Interleukin-12 / Q000097:blood / Q000235:genetics* / Q000627:therapeutic use; D015847:Interleukin-4 / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D010957:Plasmids / Q000008:administration & dosage / Q000235:genetics; D012595:Scleroderma, Systemic / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D012867:Skin / Q000473:pathology; D018417:Th1 Cells / Q000276:immunology; D018418:Th2 Cells / Q000276:immunology
D000974:Antibodies, Antinuclear; D018664:Interleukin-12; D015847:Interleukin-4; D007371:Interferon-gamma