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

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.

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.

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.