on April 1, 2004
Published online before print April 1, 2004, doi: 10.1161/01.ATV.0000127025.48140.a3
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Submitted on February 3, 2004
Accepted on March 17, 2004
Lack of Interleukin-1 Receptor Antagonist Modulates Plaque Composition in Apolipoprotein E-Deficient Mice
Kikuo Isoda *;
From Internal Medicine I (K.I., S.S., N.I., K.M., M.K., F.O.), National Defense Medical College Tokorozawa, Japan; and the Center for Experimental Medicine (T.M., Y.I.), Institute of Medical Science, University of Tokyo, Japan.
* To whom correspondence should be addressed. E-mail: isoda{at}me.ndmc.ac.jp.
Objective--Interleukin (IL)-1 plays an important role in atherosclerosis. IL-1 receptor antagonist (IL-1Ra) is an endogenous inhibitor of IL-1. However, the role of IL-1Ra in the development of atherosclerosis is poorly understood.
Methods and Results--Mice that lacked IL-1Ra (IL-1Ra-/-) were crossed with apolipoprotein E-deficient (E-/-) mice and formation of atherosclerotic lesions was analyzed after 16 weeks or 32 weeks consumption of a normal chow diet. This study focused on the comparison of atherosclerotic lesion between IL-1Ra+/+/apoE-/- (n=12) and IL-1Ra+/-/apoE-/- mice (n=12), because of the significantly leaner phenotype in IL-1Ra-/-/apoE-/- mice compared with the others. Interestingly, atherosclerotic lesion size in IL-1Ra+/-/apoE-/- mice at age 16 weeks was significantly increased (30%) compared with IL-1Ra+/+/apoE-/- mice (P<0.05). At 32 weeks, the differences of lesion size between these mice failed to achieve statistical significance. However, immunostaining demonstrated an 86% (P<0.0001) increase in the MOMA-2-stained lesion area of IL-1Ra+/-/apoE-/- mice. In addition, 
-actin staining in these lesions was significantly decreased (-15%) compared with those in IL-1Ra+/+/apoE-/- mice (P<0.05).
Conclusions--These results suggest an important role of IL-1Ra in the suppression of lesion development during early atherogenesis and furthermore indicate its role in the modulation of plaque composition.
Key words: atherosclerosis • immune system • inflammation • interleukins • macrophage
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