Leukocyte-derived interleukin 10 is required for protection against atherosclerosis in low-density lipoprotein receptor knockout mice

Arterioscler Thromb Vasc Biol. 2004 Aug;24(8):1474-8. doi: 10.1161/01.ATV.0000134378.86443.cd. Epub 2004 Jun 3.


Background: Atherosclerosis is an immunoinflammatory disease. Here we examined the role of leukocyte-derived interleukin 10 (IL-10) on advanced atherosclerosis development in low-density lipoprotein receptor knockout (LDLr-/-) mice.

Methods and results: Bone marrow cells harvested from C57BL/6 IL-10-/- and IL-10+/+ mice were transplanted into irradiated male LDLr-/- mice. Four weeks after transplantation, mice were fed a high-fat cholate-free diet for 14 weeks. Despite no differences in weights, serum total, and HDL-cholesterol levels between the 2 groups, IL-10 deficiency in leukocytes induced a >2-fold increase in lesion development in the thoracic aorta compared with controls. We also found a significant 35% increase in aortic root lesion area of IL-10-/- mice compared with IL-10+/+ mice. Furthermore, IL-10 deficiency led to a marked increase in lymphocyte and macrophage accumulation associated with a significant reduction in collagen accumulation. Finally, transfer of IL-10-/- splenocytes to LDLr-/- mice resulted in a 3-fold increase in lesion size in the aortic sinus compared with mice transplanted with IL-10+/+ splenocytes.

Conclusions: IL-10 expressed by leukocytes prevents exaggerated advanced atherosclerosis development and plays a critical role in modulation of cellular and collagen plaque composition, at least in part, through a modulation of the systemic immune response.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / pathology
  • Aortic Diseases / genetics
  • Aortic Diseases / immunology
  • Aortic Diseases / pathology
  • Aortic Diseases / prevention & control
  • Aortitis / immunology
  • Aortitis / pathology
  • Arteriosclerosis / blood
  • Arteriosclerosis / genetics
  • Arteriosclerosis / immunology
  • Arteriosclerosis / pathology
  • Arteriosclerosis / prevention & control*
  • Bone Marrow Transplantation
  • Collagen / metabolism
  • Endothelium, Vascular / pathology
  • Female
  • Fibrosis
  • Inflammation
  • Interleukin-10 / physiology*
  • Leukocytes / metabolism*
  • Lymphocytes / metabolism
  • Lymphocytes / pathology
  • Macrophages / metabolism
  • Macrophages / pathology
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Muscle, Smooth, Vascular / pathology
  • Radiation Chimera
  • Receptors, LDL / deficiency*
  • Receptors, LDL / genetics
  • T-Lymphocytes / transplantation
  • Th1 Cells / immunology


  • Receptors, LDL
  • Interleukin-10
  • Collagen