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

Objective: We examined the role of IL-1 alpha and IL-1 beta 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-1 alpha. or IL-1 beta deficient mice. IL-1 alpha KO resulted in a comparatively higher total cholesterol levels, compared to WT and IL-1 beta KO mice (398 +/- 10; 266 +/- 19; 223 +/- 13mg/dl, respectively, p < 0.001), due to higher non-HDL cholesterol. Nevertheless, aortic sinus lesion area was 56% lower in IL-1 alpha KO (p < 0.05) and 50% lower in ILAP KO(p=0.08), compared to WT mice. Likewise, SAA levels in IL-1 alpha KO mice were markedly lower compared to WT and IL-1 beta KO mice (31 +/- 14; 220 +/- 33 and 106 +/- 39 mu g/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-1 alpha-/- or IL-1 beta-/- bone marrow cells. Despite similar lipoprotein levels, aortic sinus lesion area was 59% lowerin IL-1 alpha--/- transplanted (P < 0.05) compared to IL-1+/+ transplanted mice. Lesion area in IL-1 beta-/- 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-1 alpha. Furthermore, we showed that the expression of IL-1 alpha in cells other than the bone marrow plays a significant role in non-HDL cholesterol metabolism. (c) 2006 Elsevier Ireland Ltd. All rights reserved.