Abstract 459: Attenuation of Experimental Atherosclerosis by Systemic Administration of Interleukin-19
Introduction: IL-19 is a newly described Th2 interleukin which had previously been ascribed to be inflammatory cell-specific. Ours is the only laboratory to investigate a role for this interleukin in vascular biology. The hypothesis of this study is that IL-19 can attenuate atherosclerosis through the potential mechanism of dampening leukocyte-endothelial cell interactions.
Methods and Results: IL-19 is not detected in normal artery, but is highly expressed in multiple cell types in atherosclerotic plaque suggesting a role for this interleukin in development of atherosclerosis. Five month old LDLR-/- mice were fed an atherogenic diet and injected i.p. with either 1.0ng/g/day IL-19, 10.0ng/g/day IL-19, or PBS for 12 weeks. Mice receiving systemic IL-19 injections developed significantly less atherosclerotic plaque in the aortic arch compared with control mice (17.7+/-1.7% vs 5.3+/-1.1%, p<0.0001 for 1.0ng/g/day, and 18.5+/-1.5% vs 2.2+/-0.3%, p<0.0001 for 10.0ng/g/day). To determine if IL-19 could cause plaque regression, 10.0ng/g/day IL-19 or PBS was administered to LDLR-/- mice which had previously been fed an atherogenic diet for 14 weeks. After 8 weeks of treatment, a significant difference of p<0.0025 between the no treatment and PBS groups, and a significant difference of p<0.0014 between PBS and IL-19 treated groups was noted, but no significant difference between the no treatment and IL-19 treated groups was observed. No difference in serum cholesterol, triglycerides, or body weight was noted between the control and IL-19 groups. Immunohistochemical staining of the aortic root from these mice for the macrophage marker F4/80 demonstrates IL-19 treated mice have significantly less macrophage infiltrate compared with mice injected with PBS (36.3+/-2.3% vs 20.0+/-2.7%, p<0.0004). Wild-type mice were fed an atherogenic diet and injected with 1.0ng/g/day IL-19 for 12 weeks, and intravital microscopy of leukocyte adhesion indicates that IL-19 decreases leukocyte-endothelial cell interactions in vivo.
Conclusion: When taken together, these data suggest an important role for IL-19 in inhibition, but not regression, of atherosclerotic plaque in vivo. A potential mechanism is that IL-19 can decrease leukocyte-endothelial cell interaction.
- © 2012 by American Heart Association, Inc.