Reduced atherosclerosis and inflammatory cytokines in apolipoprotein-E-deficient mice lacking bone marrow-derived interleukin-1α

Biochem Biophys Res Commun. 2011 Feb 11;405(2):197-203. doi: 10.1016/j.bbrc.2011.01.008. Epub 2011 Jan 8.


Objective: Interleukin (IL)-1α and IL-1β are products of macrophages, endothelial cells and vascular smooth muscle cells; moreover, each of these cell types is affected by the pro-inflammatory properties of both IL-1's. Whereas several studies demonstrate the proatherogenic properties of IL-1β, the role of IL-1α in atherogenesis remains unclear. We assessed whether IL-1α and IL-1β from tissue resident vascular cells or emigrating bone marrow-derived cells promote the development of atherosclerosis in apoE-/- mice and determined the effect of selective macrophage IL-1α or IL-1β deficiency on degradation of LDL and cytokine production.

Methods: We generated strains of double knock-out (KO) mice (apoE-/-/IL-1α-/- and apoE-/-/IL-1β-/-) and created chimeras consisting of apoE-/- mice reconstituted with bone marrow-derived cells from apoE-/-/IL-1+/+, apoE-/-/IL-1α-/- and apoE-/-/IL-1β-/-.

Results: The areas of aortic sinus lesions were lower in either double KO mice compared to solely apoE-/- mice, despite higher non-HDL cholesterol levels. Importantly, selective deficiency of IL-1α or IL-1β in bone marrow-derived cells inhibited atherogenesis to the same extent as in double KO mice without affecting plasma lipids. Aortic sinus lesions in apoE-/- mice transplanted with IL-1β-/- or IL-1α-/- cells were 32% and 52% lower, respectively, than in IL-1+/+ transplanted mice. Ex vivo, isolated IL-1α-/- macrophages from atherosclerotic mice degraded LDL and secreted IL-6, TNFα and IL-12 similarly to IL-1+/+ macrophages; however, IL-1α deficient macrophages secreted reduced levels of IL-1β (-50%) and 2-3-fold higher levels of the anti-inflammatory cytokine IL-10.

Conclusion: We show for the first time that it is IL-1α from bone marrow-derived cells that accelerates atherogenesis in apoE-deficient mice rather than constitutive IL-1α in vascular cells, possibly by increasing the inflammatory cytokine profile of macrophages.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apolipoproteins E / genetics
  • Atherosclerosis / genetics
  • Atherosclerosis / metabolism*
  • Atherosclerosis / pathology
  • Bone Marrow / metabolism*
  • Cytokines / antagonists & inhibitors*
  • Foam Cells / metabolism
  • Interleukin-1alpha / genetics
  • Interleukin-1alpha / metabolism*
  • Interleukin-1beta / genetics
  • Interleukin-1beta / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Mice, Mutant Strains


  • Apolipoproteins E
  • Cytokines
  • Interleukin-1alpha
  • Interleukin-1beta