Differential role and tissue specificity of interleukin-1alpha gene expression in atherogenesis and lipid metabolism

Atherosclerosis. 2007 Nov;195(1):31-8. doi: 10.1016/j.atherosclerosis.2006.11.026. Epub 2006 Dec 14.


Objective: We examined the role of IL-1alpha and IL-1beta expressed by bone marrow-derived cells in atherogenesis and lipid metabolism.

Methods and results: We first studied the effect of atherogenic diet on wild-type C57BL/6 IL-1alpha or IL-1beta deficient mice. IL-1alpha KO resulted in a comparatively higher total cholesterol levels, compared to WT and IL-1beta KO mice (398+/-10; 266+/-19; 223+/-13 mg/dl, respectively, p<0.001), due to higher non-HDL cholesterol. Nevertheless, aortic sinus lesion area was 56% lower in IL-1alpha KO (p<0.05) and 50% lower in IL-1beta KO (p=0.08), compared to WT mice. Likewise, SAA levels in IL-1alpha KO mice were markedly lower compared to WT and IL-1beta KO mice (31+/-14; 220+/-33 and 106+/-39 microg/ml, respectively, p<0.001). To study the specific role of bone marrow-derived IL-1, irradiated C57BL/6 mice were transplanted with either IL-1+/+, IL-1alpha-/- or IL-1beta-/- bone marrow cells. Despite similar lipoprotein levels, aortic sinus lesion area was 59% lower in IL-1alpha-/- transplanted (p<0.05) compared to IL-1+/+ transplanted mice. Lesion area in IL-1beta-/- was 33% lower than in IL-1+/+ recipient mice, but it was not statistically significant.

Conclusion: We demonstrated that early lesion formation is accelerated specifically by bone marrow-derived IL-1alpha. Furthermore, we showed that the expression of IL-1alpha in cells other than the bone marrow plays a significant role in non-HDL cholesterol metabolism.

MeSH terms

  • Amyloid / blood
  • Amyloid / chemistry
  • Animals
  • Atherosclerosis / pathology*
  • Bone Marrow Transplantation
  • Cholesterol, HDL / metabolism
  • Gene Expression Regulation*
  • Interleukin-1alpha / biosynthesis*
  • Interleukin-1beta / biosynthesis
  • Lipid Metabolism*
  • Lipids / chemistry*
  • Lipoproteins / chemistry
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout


  • Amyloid
  • Cholesterol, HDL
  • Interleukin-1alpha
  • Interleukin-1beta
  • Lipids
  • Lipoproteins