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

Biochem Biophys Res Commun. 2001 Jan 26;280(3):707-12. doi: 10.1006/bbrc.2000.4171.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antibodies, Antinuclear / blood
  • Genetic Therapy
  • Injections, Intramuscular
  • Interferon-gamma / blood
  • Interleukin-12 / blood
  • Interleukin-12 / genetics*
  • Interleukin-12 / therapeutic use
  • Interleukin-4 / blood
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains
  • Plasmids / administration & dosage
  • Plasmids / genetics
  • Scleroderma, Systemic / genetics
  • Scleroderma, Systemic / immunology
  • Scleroderma, Systemic / pathology
  • Scleroderma, Systemic / therapy*
  • Skin / pathology
  • Th1 Cells / immunology
  • Th2 Cells / immunology


  • Antibodies, Antinuclear
  • Interleukin-12
  • Interleukin-4
  • Interferon-gamma