Abstract 13911: Interleukin-5-induced Eosinophil Population Improves Cardiac Function After Myocardial Infarction

Background: Eosinophils have been commonly recognized as one of the major participants in helminth infection and allergic diseases. Recent studies suggest that these innate immune cells mediate tissue repairs after muscle, hepatic, or endometrial injuries. Yet, the precise role of eosinophils in myocardial infarction (MI) remains unclear. Interleukin (IL)-5 is the most important cytokines that are responsible for the development, activation, and survival of eosinophils. Here, we report a role of IL-5 in infarcted heart. Methods and Results: MI was induced by permanent ligation of left anterior descending coronary artery in wild-type C57BL/6 mice. Western blot show that infarcted heart IL-5 expression is increased by 2.35-fold (P<0.01) higher than their expression in the heart of sham mice at day 5 after surgery. External supply of recombinant mouse IL-5 (100 μg/kg/day for 3 days) reduces the infarct size (by 13.38%, P<0.01), increases ejection fraction (from 32.41% to 43.93%, P<0.01), and increases angiogenesis (CD31 area from 3.35% to 4.14%, P=0.03) in the peri-infarct zone. An expansion of eosinophils is observed in both the peripheral blood and infarcted myocardium after IL-5 administration. Pharmacological depletion of eosinophils by TRFK5 pretreatment mutes the beneficial effects of IL-5 in MI mice. Mechanistic studies also demonstrate that IL-5 increases the accumulation of M2 macrophages in infarcted myocardium at day 7 post-MI. In vitro co-culture experiments reveal that eosinophils shift bone marrow-derived macrophage polarization towards the M2 phenotypes. This effect is abolished by IL-4 neutralizing antibody, but not IL-10 or IL-13 neutralization. Western blot analyses show that eosinophils promote the macrophage downstream STAT6 phosphorylation. Conclusions: We demonstrate here that IL-5 facilitates the recovery of post-MI cardiac function by promoting eosinophils accumulation and subsequent polarization of M2 macrophages via the IL-4/STAT6 axis.