Interleukin-19 can enhance angiogenesis by Macrophage Polarization

Hypoxia in ischemic limbs typically initiates angiogenic and inflammatory factors to promote angiogenesis in attempt to restore perfusion, and revascularization involves multiple cell types and systems. Macrophage display phenotype plasticity, and can polarize in response to local and systemic cytokine stimuli. M2 macrophage are known to play an important role in angiogenesis and wound healing. While accepted that many pro-inflammatory cytokines induce angiogenesis, the effects of anti-inflammatory interleukins on initiation of angiogenesis are less clear. Interleukin-19 [IL-19] is a presumed anti-inflammatory cytokine, with unknown effects on macrophage polarization. In our recent study, we used several experimental approaches and determined that IL-19 regulated neovascularization in the murine hind-limb ischemia model. In addition to endothelial cells, we found that IL-19 could target and polarize macrophage to the M2 phenotype. IL-19 could induce expression of angiogenic, and reduce expression of anti-angiogenic cytokines in these cells. This is the first study to demonstrate that IL-19 could polarize macrophage, and potentially identifies IL-19 as a therapy to induce angiogenesis in ischemic tissue.