Interferon‐β Modulates Inflammatory Response in Cerebral Ischemia

• Published in: Journal of the American Heart Association 2016-01, Vol.5 (1), p.n/a
• Main Authors: Kuo, Ping‐Chang, Scofield, Barbara A., Yu, I‐Chen, Chang, Fen‐Lei, Ganea, Doina, Yen, Jui‐Hung
• Format: Article
• Language: English
• Subjects: Animals; Anti-Inflammatory Agents - pharmacology; Brain - drug effects; Brain - immunology; Brain - metabolism; Brain - pathology; CD4+ T cells; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - metabolism; Cell Adhesion Molecules - metabolism; Cell Line; Chemotaxis, Leukocyte - drug effects; Disease Models, Animal; Endothelial Cells - drug effects; Endothelial Cells - immunology; Endothelial Cells - metabolism; Infarction, Middle Cerebral Artery - immunology; Infarction, Middle Cerebral Artery - metabolism; Infarction, Middle Cerebral Artery - pathology; Infarction, Middle Cerebral Artery - prevention & control; Inflammation Mediators - metabolism; Interferon-beta - pharmacology; Interferon‐β; ischemic stroke; Macrophages - drug effects; Macrophages - immunology; Macrophages - metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; microglia; Microglia - drug effects; Microglia - immunology; Microglia - metabolism; monocytes/macrophages; neuroinflammation; Neuroprotective Agents - pharmacology; Neutrophil Infiltration - drug effects; Neutrophils - drug effects; Neutrophils - immunology; Neutrophils - metabolism; Original Research; Receptor, Interferon alpha-beta - deficiency; Receptor, Interferon alpha-beta - genetics; reperfusion; γδ T cells
• ISSN: 2047-9980; 2047-9980
• DOI: 10.1161/JAHA.115.002610

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 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.