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

Neuroscience. 2018 Aug 10:385:75-89. doi: 10.1016/j.neuroscience.2018.05.047. Epub 2018 Jun 12.

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.

Keywords: IL-33; M1 macrophage; M2 macrophage; cytokines; stroke.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Brain / drug effects
  • Brain / metabolism*
  • Brain Ischemia / drug therapy
  • Brain Ischemia / genetics
  • Brain Ischemia / metabolism*
  • Cytokines / metabolism
  • Interleukin-33 / genetics
  • Interleukin-33 / metabolism*
  • Interleukin-33 / pharmacology
  • Interleukin-33 / therapeutic use
  • Macrophages / drug effects
  • Macrophages / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Microglia / drug effects
  • Microglia / metabolism*
  • Reperfusion Injury / drug therapy
  • Reperfusion Injury / genetics
  • Reperfusion Injury / metabolism*

Substances

  • Cytokines
  • Interleukin-33