on July 21, 2003
Published online before print July 21, 2003, doi: 10.1161/01.CIR.0000085567.18648.21
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Submitted on March 12, 2003
From the First Department of Internal Medicine (K.I., M.S., N.I., K.N., M.K., F.O.), and Department of Physiology II (Y.N.), National Defense Medical College, Tokorozawa, Japan; and the Center for Experimental Medicine, Institute of Medical Science, University of Tokyo (T.M., R.H., Y.I.), Tokyo, Japan. * To whom correspondence should be addressed. E-mail: isoda{at}me.ndmc.ac.jp.
Background--The cytokine interleukin (IL)-1 is an important mediator of inflammation and cardiovascular disease. Activity of this cytokine is modulated endogenously via the IL-1 receptor antagonist (IL-1Ra). The role of IL-1Ra in neointima formation after injury, however, is poorly understood. Methods and Results--Using IL-1Ra-deficient (IL-1Ra-/-; backcrossed 8 generations into the C57BL/6J background) and wild-type (IL-1Ra+/+) mice, we investigated neointimal formation 3 weeks after femoral artery injury induced by an external vascular cuff model. Intima and media thicknesses were measured, and the intima/media ratio was calculated. The mean intimal thickness and the intima/media ratio of IL-1Ra-/- mice increased by 249% (31.8±2.9 µm [n=10] versus 9.1±0.7 µm [n=10]; P<0.0001) and 257% (2.5±0.2 versus 0.7±0.1; P<0.0001), respectively, compared with IL-1Ra+/+ mice. No significant differences were observed in the medial thickness. Control immunostaining for IL-1Ra in injured vessels localized IL-1 Conclusions--The absence of IL-1Ra promotes neointimal formation in mice after injury. These results suggest that endogenous IL-1Ra may suppress other occlusive vascular responses to injury, such as atherosclerosis and restenosis after angioplasty.
Revised on June 12, 2003
Accepted on June 13, 2003
Deficiency of Interleukin-1 Receptor Antagonist Promotes Neointimal Formation After Injury
Kikuo Isoda MD, PhD*,
and the endogenous inhibitor in the endothelium and inflammatory cells of the adventitia in IL-1Ra+/+ but not IL-1Ra-/- mice.
Key words: genes • inflammation • interleukins
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