Attenuation of atherogenesis by systemic and local adenovirus-mediated gene transfer of interleukin-10 in LDLr-/- mice

FASEB J. 2001 Dec;15(14):2730-2. doi: 10.1096/fj.01-0483fje. Epub 2001 Oct 29.


In view of its multifaceted anti-inflammatory properties, interleukin-10 (IL-10) has been deemed to be potentially anti-atherogenic. We have evaluated the capacity of adenoviral gene transfer of IL-10 for the modulation of de novo atherosclerotic lesion formation by systemic and by local overexpression. Atherogenesis was initiated in the carotid arteries of low-density lipoprotein receptor deficient mice by perivascular placement of silastic collars. One week after collar placement, mice were injected intravenously with 1 x 109 plaque-forming units (pfu's) of IL-10 (AdV.IL-10) or control adenovirus (AdV.empty). Administration of AdV.IL-10 resulted in extended systemic expression of IL-10 (peak serum level 3.0 +/- 1.1 ng/ml) and a reduction in atherosclerotic lumen stenosis by 62.2% (P<0.02). This finding was accompanied by monocyte deactivation and lowering of serum cholesterol levels (maximum decrease 44%). In a second experiment, collared arteries were transfected locally by transluminal instillation of adenovirus (titer 1.5x1010 pfu/ml). Systemic parameters remained unchanged following local transfection, but the degree of stenosis was, nonetheless, decreased by 44.9% (P<0.05). We conclude that a marked inhibition of atherogenesis can be achieved by systemic overexpression of AdV.IL-10, owing to its metabolic and immunomodulatory effects. Local IL-10 transfer is virtually equipotent, however, and it may represent a valuable addition to the armory of anti-atherosclerotic therapies.

MeSH terms

  • Adenoviridae / genetics
  • Animals
  • Arteriosclerosis / genetics
  • Arteriosclerosis / pathology
  • Arteriosclerosis / therapy*
  • Carotid Artery Diseases / genetics
  • Carotid Artery Diseases / pathology
  • Carotid Artery Diseases / therapy
  • Cholesterol / blood
  • Constriction
  • Female
  • Gene Expression Regulation
  • Gene Transfer Techniques
  • Genetic Therapy*
  • Genetic Vectors / administration & dosage
  • Genetic Vectors / genetics
  • Humans
  • Interleukin-10 / blood
  • Interleukin-10 / genetics*
  • Interleukin-10 / therapeutic use
  • Macrophages / pathology
  • Mice
  • Mice, Knockout
  • Monocytes / immunology
  • Monocytes / metabolism
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Receptors, Interleukin / genetics
  • Receptors, Interleukin-10
  • Receptors, LDL / deficiency
  • Receptors, LDL / genetics*
  • Tumor Necrosis Factor-alpha / metabolism


  • RNA, Messenger
  • Receptors, Interleukin
  • Receptors, Interleukin-10
  • Receptors, LDL
  • Tumor Necrosis Factor-alpha
  • Interleukin-10
  • Cholesterol