Intramuscular gene transfer of interleukin-10 cDNA reduces atherosclerosis in apolipoprotein E-knockout mice

Atherosclerosis. 2004 Jan;172(1):21-9. doi: 10.1016/j.atherosclerosis.2003.08.032.


Atherosclerosis has a close relationship to inflammation, particularly T helper type 1 lymphocyte (Th1) response. Interleukin-10 (IL-10), is thought to suppress Th1 response. To target therapeutic strategy for atherosclerosis, we tested whether IL-10 gene transfer suppresses atherosclerosis in apolipoprotein E-knockout (apoE-KO) mice. Four-week-old apoE-KO mice were divided into two groups and either murine IL-10 cDNA plasmid or empty control vector was transferred to the femoral muscle with the use of Hemagglutinating virus of Japan (HVJ)-liposome. At 1 week after transfection, high cholesterol diet was started and continued for 8 weeks. After euthanasia, histological studies of atherosclerotic lesions and quantitative RT-PCR for Th1 cytokines (IL-12 and IFN-gamma) in spleens were performed. IL-10 cDNA gene transfer to the muscle increased plasma IL-10 levels and depressed expression of Th1 cytokines without changing plasma cholesterol levels. IL-10 gene transfer significantly reduced the atherosclerotic plaque area and the macrophage infiltrated area. IL-12 and IFN-gamma mRNA expressions in spleens and plasma IFN-gamma levels were decreased by IL-10 gene transfer. Therefore, IL-10 gene transfer changed the Th1 response and suppressed atherosclerotic lesion formation in apoE-KO mice. IL-10 could be a new target as a therapeutic tool for the treatment of atherosclerosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics*
  • Arteriosclerosis / therapy*
  • DNA, Complementary*
  • Gene Transfer Techniques*
  • Genetic Therapy / methods
  • Genetic Vectors
  • Interferon-gamma / genetics
  • Interleukin-10 / genetics*
  • Interleukin-12 / genetics
  • Liposomes
  • Male
  • Mice
  • Mice, Knockout
  • Plasmids
  • RNA, Messenger / analysis
  • Reverse Transcriptase Polymerase Chain Reaction
  • Sendai virus / genetics


  • Apolipoproteins E
  • DNA, Complementary
  • Liposomes
  • RNA, Messenger
  • Interleukin-10
  • Interleukin-12
  • Interferon-gamma