IL-4/STAT6 signaling facilitates innate hematoma resolution and neurological recovery after hemorrhagic stroke in mice

Significance Hemorrhagic stroke, resulting from intracerebral hemorrhage, is a devastating medical condition currently without effective cure. Here we report that intranasal delivery of IL-4, a well-known antiinflammatory cytokine, facilitates microglia- and macrophage-mediated hematoma resolution and improves long-term functional recovery in two different mouse models of intracerebral hemorrhage. Mechanistically, IL-4 activates a signaling cascade involving signal transducer and activator of transcription 6 and IL-1 receptor-like 1, thereby enhancing the phagocytotic capability of microglia and macrophages to remove red blood cells from intracerebral hematomata. Our in vitro and in vivo preclinical studies support the view that IL-4 treatment has the therapeutic potential to promote hematoma resolution and functional restoration in hemorrhagic stroke victims.