Interferon-β modulates inflammatory response in cerebral ischemia

Ping Chang Kuo, Barbara A. Scofield, I. Chen Yu, Fen Lei Chang, Doina Ganea, Jui Hung Yen

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

Background-Stroke is a leading cause of death in the world. In > 80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon-β (IFNβ), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing-remitting multiple sclerosis for more than a decade. Its anti-inflammatory properties and well-characterized safety profile suggest that IFNβ has therapeutic potential for the treatment of ischemic stroke. Methods and Results-We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNb not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNb modulates ischemic brain inflammation were identified. IFNb reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4+ T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Conclusions-Our results demonstrate that IFNβ exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNβ is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator.

Original languageEnglish (US)
Article numbere002610
JournalJournal of the American Heart Association
Volume5
Issue number1
DOIs
StatePublished - Jan 1 2016

Keywords

  • CD4 T cells
  • Interferon-β
  • Ischemic stroke
  • Microglia
  • Monocytes/macrophages
  • Neuroinflammation
  • Reperfusion
  • γδ T cells

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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