Interleukin-13 deficiency aggravates healing and remodeling in male mice after experimental myocardial infarction.

ABSTRACT

BACKGROUND: Activation of innate immunity, especially infiltration of monocytes, is critical for proper wound healing and scar formation after myocardial infarction (MI). Therefore, we tested the hypothesis that interleukin-13 (IL-13), which influences the differentiation of monocytes/macrophages and has profibrotic properties, modulates wound healing and remodeling after MI. METHODS AND RESULTS: MI was induced by permanent ligation of the left coronary artery in both male and female wild-type (WT)/IL-13(-/-) mice. Real-time polymerase chain reaction demonstrated that expression of IL-13 was induced in left and right ventricular myocardium of WT mice within days in response to MI. Fifty-six-day survival was significantly impaired (65% in WT versus 34% in IL-13(-/-)) in male but not female IL-13(-/-) (55% in WT versus 54% in IL-13(-/-)) mice. Serial echocardiography showed significantly increased left ventricular dilation in male IL-13(-/-) compared with WT mice starting from day 1 after MI, despite comparable infarct size. Fluorescence-activated cell sorter analysis revealed less leukocyte infiltration in male IL-13(-/-) mice on day 3. Real-time polymerase chain reaction analysis demonstrated reduced expression of marker genes of alternative activation in monocytes sorted from the infarct zone of male IL-13(-/-) in comparison with WT mice on day 3 after MI. CONCLUSIONS: Genetic deficiency of IL-13 worsens outcome after MI in male mice. Our data indicate that IL-13 regulates leukocyte recruitment and induces M2-like monocyte/macrophage differentiation, which modifies wound healing within the infarct zone.