11 Citations (Scopus)

Abstract

Acute ischemic stroke is followed by a complex interplay between the brain and the immune system in which ischemia-reperfusion leads to a detrimental inflammatory response that causes brain injury. In the brain, IL-15 is expressed by astrocytes, neurons and microglia. Previous study showed that ischemia-reperfusion induces expression of IL-15 by astrocytes. Transgenic over-expression of IL-15 in astrocytes aggravates ischemia-reperfusion brain damage by increasing the levels and promoting the effector functions of CD8+ T and NK cells. Treatment of neonatal rats with IL-15 neutralizing antibody before hypoxia-ischemia induction reduces the infarct volume. However, as stroke-induced inflammatory responses differ between neonate and adult brain, the effects of IL-15 blockade on the injury and immune response arising from stroke in adult animals has remained unclear. In this study, we examined the effect of post-ischemia/reperfusion IL-15 blockade on the pathophysiology of cerebral ischemia-reperfusion in adult mice. Using a cerebral ischemia-reperfusion model, we compared infarct size and the infiltrating immune cells in the brain of wild type (WT) mice and Il15−/− mice lacking NK and memory CD8+ T cells. We also evaluated the effects of IL-15 neutralizing antibody treatment on brain infarct volume, motor function, and the status of brain-infiltrating immune cells in WT mice. Il15−/− mice show a smaller infarct volume and lower numbers of activated brain-infiltrating NK, CD8+ T, and CD4+ T cells compared to WT mice after cerebral ischemia-reperfusion. Post-ischemia/reperfusion IL-15 blockade reduces infarct size and improves motor and locomotor activity. Furthermore, IL-15 blockade reduces the effector function of NK, CD8+ T, and CD4+ T cells in the ischemia-reperfusion brain of WT mice. Ablation of IL-15 responses after cerebral ischemia-reperfusion ameliorates brain injury in adult mice. Therefore, targeting IL-15 is a potential effective therapy for ischemic stroke.

Original languageEnglish
Pages (from-to)562-570
Number of pages9
JournalBrain, Behavior, and Immunity
Volume73
DOIs
Publication statusPublished - Oct 1 2018

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Keywords

  • Cerebral ischemia-reperfusion
  • IL-15
  • IL-15 antibody
  • Immune response

ASJC Scopus subject areas

  • Immunology
  • Endocrine and Autonomic Systems
  • Behavioral Neuroscience

Cite this

Lee, G. A., Lin, T. N., Chen, C. Y., Mau, S. Y., Huang, W. Z., Kao, Y. C., Ma, R. Y., & Liao, N. S. (2018). Interleukin 15 blockade protects the brain from cerebral ischemia-reperfusion injury. Brain, Behavior, and Immunity, 73, 562-570. https://doi.org/10.1016/j.bbi.2018.06.021