Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia

Ana Rita Inacio, Yawei Liu, Bettina Hjelm Clausen, Martina Svensson, Krzysztof Kucharz, Yiyi Yang, Totte Stankovich, Reza M. H. Khorooshi, Kate Lykke Lambertsen, Shohreh Issazadeh-Navikas, Tomas Deierborg

Research output: Contribution to journalJournal articleResearchpeer-review

Abstract

Background: Interferon (IFN)-β exerts anti-inflammatory effects, coupled to remarkable neurological improvements in multiple sclerosis, a neuroinflammatory condition of the central nervous system. Analogously, it has been hypothesized that IFN-β, by limiting inflammation, decreases neuronal death and promotes functional recovery after stroke. However, the core actions of endogenous IFN-β signaling in stroke are unclear. Methods: To address this question, we used two clinically relevant models of focal cerebral ischemia, transient and permanent middle cerebral artery occlusion, and two genetically modified mouse lines, lacking either IFN-β or its receptor, the IFN-α/β receptor. Subsets of inflammatory and immune cells isolated from the brain, blood, and spleen were studied using flow cytometry. Sensorimotor deficits were assessed by a modified composite neuroscore, the rotating pole and grip strength tests, and cerebral infarct volumes were given by lack of neuronal nuclei immunoreactivity. Results: Here, we report alterations in local and systemic inflammation in IFN-β knockout (IFN-βKO) mice over 8 days after induction of focal cerebral ischemia. Notably, IFN-βKO mice showed a higher number of infiltrating leukocytes in the brain 2 days after stroke. Concomitantly, in the blood of IFN-βKO mice, we found a higher percentage of total B cells but a similar percentage of mature and activated B cells, collectively indicating a higher proliferation rate. The additional differential regulation of circulating cytokines and splenic immune cell populations in wild-type and IFN-βKO mice further supports an important immunoregulatory function of IFN-β in stroke. Moreover, we observed a significant weight loss 2-3 days and a reduction in grip strength 2 days after stroke in the IFN-βKO group, while endogenous IFN-β signaling did not affect the infarct volume. Conclusions: We conclude that endogenous IFN-β signaling attenuates local inflammation, regulates peripheral immune cells, and, thereby, may contribute positively to stroke outcome.

Original languageEnglish
Article number211
JournalJournal of Neuroinflammation
Volume12
Number of pages18
ISSN1742-2094
DOIs
Publication statusPublished - 18. Nov 2015

Keywords

  • Cytokines
  • IFN-α/β receptor
  • Inflammatory and immune cells
  • Interferon-β
  • Knockout mice
  • Middle cerebral artery occlusion
  • Male
  • Ischemic Attack, Transient/pathology
  • Hand Strength/physiology
  • Brain/pathology
  • Infarction, Middle Cerebral Artery/pathology
  • Receptors, Interferon/genetics
  • Brain Ischemia/pathology
  • Inflammation/pathology
  • Spleen/cytology
  • Mice, Inbred C57BL
  • Interferon-beta/genetics
  • Cytokines/blood
  • Mice, Knockout
  • B-Lymphocytes/pathology
  • Animals
  • Stroke/pathology
  • Lymphocyte Count
  • Mice
  • Leukocytes/pathology
  • Postural Balance

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