Deficiency of Interleukin-1 Receptor Antagonist Promotes Neointimal Formation After Injury

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-1β and the...