title: Interferon-β Modulates Inflammatory Response in Cerebral Ischemia.
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.
  
  
  RESULTS
  We investigated the therapeutic effect of IFNβ in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNβ not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNβ modulates ischemic brain inflammation were identified. IFNβ 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.
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN (P.C.K., B.A.S., J.H.Y.).
authors.forename: Ping-Chang
authors.initials: PC
authors.lastname: Kuo
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN (P.C.K., B.A.S., J.H.Y.).
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Scofield
authors.affiliation: Department of Anatomy and Cell Biology, Indiana University School of Medicine, Fort Wayne, IN (I.C.Y.).
authors.forename: I-Chen
authors.initials: IC
authors.lastname: Yu
authors.affiliation: Department of Neurology, Indiana University School of Medicine, Fort Wayne, IN (F.L.C.).
authors.forename: Fen-Lei
authors.initials: FL
authors.lastname: Chang
authors.affiliation: Department of Microbiology and Immunology, Temple University School of Medicine, Philadelphia, PA (D.G.).
authors.forename: Doina
authors.initials: D
authors.lastname: Ganea
authors.affiliation: Department of Microbiology and Immunology, Indiana University School of Medicine, Fort Wayne, IN (P.C.K., B.A.S., J.H.Y.).
authors.forename: Jui-Hung
authors.initials: JH
authors.lastname: Yen
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D001921:Brain / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D015496:CD4-Positive T-Lymphocytes / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D015815:Cell Adhesion Molecules / Q000378:metabolism; D002460:Cell Line; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D004195:Disease Models, Animal; D042783:Endothelial Cells / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D020244:Infarction, Middle Cerebral Artery / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D018836:Inflammation Mediators / Q000378:metabolism; D016899:Interferon-beta / Q000494:pharmacology*; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017628:Microglia / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D018696:Neuroprotective Agents / Q000494:pharmacology*; D020556:Neutrophil Infiltration / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D053633:Receptor, Interferon alpha-beta / Q000172:deficiency / Q000235:genetics
chemical_list: D000893:Anti-Inflammatory Agents; D015815:Cell Adhesion Molecules; C508032:Ifnar1 protein, mouse; D018836:Inflammation Mediators; D018696:Neuroprotective Agents; D053633:Receptor, Interferon alpha-beta; D016899:Interferon-beta
keywords: CD4+ T cells; Interferon‐β; ischemic stroke; microglia; monocytes/macrophages; neuroinflammation; reperfusion; γδ T cells