Interleukin-33 Protects Ischemic Brain Injury by Regulating Specific Microglial Activities

Abstract Interleukin-33 (IL-33), a novel member of the IL-1 family, expressed in many tissue and cell types, is involved in inflammation and immune functions. Previous studies suggest that IL-33 may play a role in ischemic stroke. Here, we evaluated the effect of IL-33 in cerebral ischemia–reperfusion-induced injury and investigated its underlying mechanism. Our data indicated that IL-33 deficiency exacerbated the neurological dysfunction caused by cerebral ischemia–reperfusion injury in mice and led to the formation of larger cerebral infarct volume as shown by 2,3,5-triphenyltetrazolium chloride staining and magnetic resonance imaging. Furthermore, the M1 and M2 macrophage-like microglial immune responses with decreased expression of the corresponding cytokines were seen in IL-33-deficient mice. IL-33 deficiency led to more biased to M2-like activities. The aggravated cerebral ischemia–reperfusion injury in IL-33-deficient mice is partially restored by intracerebroventricular injection of IL-33. These data suggest that IL-33 promotes the amplification of macrophage polarization and cytokine production associated with M2 macrophage-like microglial immune phenotype, which may contribute to the protective effects in the ischemic stroke, and that IL-33 may be a potential therapeutic target for ischemic stroke.