Beneficial potential of intravenously administered IL-6 in improving outcome after murine experimental stroke

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Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with neuroprotective properties. Still, the therapeutic potential of IL-6 after experimental stroke has not yet been investigated in a clinically relevant way. Here, we investigated the therapeutic use of intravenously administered IL-6 and the soluble IL-6 receptor (sIL-6R) alone or in combination, early after permanent middle cerebral artery occlusion (pMCAo) in mice. IL-6 did not affect the infarct volume in C57BL/6 mice, at neither 24 nor 72 h after pMCAo but reduced the infarct volume in IL-6 knockout mice at 24 h after pMCAo. Assessment of post-stroke behavior showed an improved grip strength after a single IL-6 injection and also improved rotarod endurance after two injections, in C57BL/6 mice at 24 h. An improved grip strength and a better preservation of sensory functions was also observed in IL-6 treated IL-6 knockout mice 24 h after pMCAo. Co-administration of IL-6 and sIL-6R increased the infarct volume, the number of infiltrating polymorphonuclear leukocytes and impaired the rotarod endurance ofC57BL/6mice 24 h after pMCAo. IL-6 administration to naïve C57BL/6 mice lead after 45 minutes to increased plasma-levels of CXCL1 and IL-10, whereas IL-6 administration to C57BL/6 mice lead to a reduction in the ischemia-induced increase in IL-6 and CXCL1 at both mRNA and protein level in brain, and of IL-6 and CXCL1 in serum. We also investigated the expression of IL-6 and IL-6R after pMCAo and found that cortical neurons upregulated IL-6 mRNA and protein, and also upregulated the IL-6R after pMCAo. In conclusion, the results show a complex but potentially beneficial effect of intravenously administered IL-6 in experimental stroke.

Original languageEnglish
JournalBrain, Behavior, and Immunity
Volume65
Pages (from-to)296-311
ISSN0889-1591
DOIs
Publication statusPublished - Oct 2017

Keywords

  • Journal Article
  • Interleukin-6 receptor
  • Permanent middle cerebral artery occlusion
  • Cytokines
  • Neutrophils
  • Focal cerebral ischemia
  • CXCL1
  • Inflammation
  • gp130
  • Chemokines
  • IL-10
  • Male
  • Infarction, Middle Cerebral Artery/metabolism
  • Cytokines/metabolism
  • Receptors, Interleukin-6/metabolism
  • Disease Models, Animal
  • Brain Ischemia/drug therapy
  • Mice, Inbred C57BL
  • Inflammation/metabolism
  • Treatment Outcome
  • Mice, Knockout
  • Animals
  • Neurons/metabolism
  • Interleukin-6/metabolism
  • Stroke/metabolism
  • Mice
  • RNA, Messenger
  • Brain/metabolism

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