IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis

Conjugated linoleic acid (CLA) induces regression of preestablished atherosclerosis in the ApoE(-/-) mouse. Understanding the mechanisms involved may help in identifying novel pathways associated with the regression of human disease. Animals were administered a 1% cholesterol diet for 12 wk, with 1% CLA supplementation from wk 8 to 12. ApoE(-/-) mice fed only the 1% cholesterol diet for 12 wk were employed as controls. Transcriptomic analysis of mouse aorta showed that many of the components of the IL-10 signaling pathway were modified during CLA-induced regression. Real-time PCR and Western blot analysis showed increased IL-10 receptor expression, phosphorylation of STAT3, and downstream target gene expression in the aorta, alongside an increase in serum IL-10 (79.8 +/- 22.4 vs. 41.9 +/- 5.5 pg/ml, n=10; P<0.01). CLA -supplementation also increased IL-10 production in bone marrow-derived macrophages (143.6 +/- 28.6 vs. 94 +/- 5.6 pg/ml, n=5; P<0.05). To explore the mechanisms for altered IL-10 production, we examined the profile of monocyte/macrophage phenotype in the vessel wall, bone marrow, and spleen. CLA increased macrophage polarization toward an anti-inflammatory M2 phenotype in vivo, increasing the population of Ly6C(lo) monocytes (29 vs. 77 +/- 14, n=5, P < 0.05) in the aorta. CLA had similar effects on monocytes/macrophages differentiated from marrow-derived progenitor cells and on splenocytes. The induction of IL-10 on CLA supplementation in this model may reflect a systemic alteration toward an anti-inflammatory phenotype, which, in turn promotes increased vascular infiltration by Ly6C(lo) monocytes. These cells may contribute to CLA-induced disease regression.-McCarthy, C., Duffy, M. M., Mooney, D., James, W. G., Griffin, M. D., Fitzgerald, D. J., Belton, O. IL-10 mediates the immunoregulatory response in conjugated linoleic acid-induced regression of atherosclerosis. FASEB J. 27, 499-510 (2013). www.fasebj.org