Attenuation of Experimental Atherosclerosis by Interleukin‐19

Abstract

Interleukin‐19 (IL‐19) is a Th2, anti‐inflammatory interleukin. IL‐19 is expressed in several cell types in human atherosclerotic plaque. We tested the hypothesis that IL‐19 can reduce atherosclerotic plaque. LDLR−/− mice injected with either 1.0ng/g/day or 10.0ng/g/day rmIL‐19 had significantly less plaque area in the aortic arch compared with controls (p<0.0001). Plaque regression studies indicated IL‐19 mice had significantly less plaque accumulation in the aortic arch compared with controls (p<0.0001), but none compared to baseline controls. IL‐19 treated mice demonstrated immune cell Th2 polarization, with decreased T‐bet and IFNã, and increased expression of GATA3 and FoxP3 mRNA. Cellular characterization of plaque demonstrated IL‐19 treated mice have significantly less macrophage infiltrate compared with controls (p<0.001). Intravital microscopy revealed significantly less leukocyte adhesion in wild‐type mice injected with IL‐19 and fed an atherogenic diet compared with controls. Treatment of cultured endothelial, vascular smooth muscle, and bone marrow‐derived macrophage with IL‐19 significantly decreased chemokine mRNA and the mRNA‐stability protein HuR. Together, these data indicate that IL‐19 is a potent inhibitor of experimental atherosclerosis, with diverse mechanisms including immune cell polarization, decrease in macrophage adhesion, and decrease in gene expression.