Abstract
Inflammatory damage following ICH is often attributed to microglia/macrophage activation. In many diseases, IL-4 has been proven to switch microglia/macrophages from the pro-inflammatory to the anti-inflammatory subtype. However, the role and underlying mechanism of IL-4 in ICH, especially in neuroprotection, remain unknown. In our study, we constructed a microglia/macrophage polarization model in BV2 cells to verify that the M2 shift of microglia/macrophages was mediated by JAK1/STAT6 after IL-4 treatment and then revealed that in vitro administration of IL-4 decreased M1 markers, pro-inflammatory cytokines and neuroapoptosis markers but significantly increased M2 markers and anti-inflammatory cytokines. Using an ICH model in mice, we observed that IL-4 administration decreased neurological deficits, brain edema and infarct lesions induced by ICH. We verified that IL-4 mediates inflammation by regulating M1/M2 polarization in ICH and explored the underlying mechanism. Furthermore, we discovered that pathway components and apoptosis-related proteins showed consistent trends based on their respective roles, and inferred that the process that TNF-α activates caspase-3 may be the crosstalk that microglia phagocytosis developed into accelerate apoptosis of cells in ICH. In conclusion, our study demonstrates that IL-4 may promote M2 microglia/macrophage polarization partly through the JAK1/STAT6 pathway to alleviate neuroinflammation after ICH.