Treatment with an interleukin-1 receptor antagonist mitigates neuroinflammation and brain damage after polytrauma

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Abstract

Traumatic brain injury (TBI) and long bone fracture are common in polytrauma. This injury combination in mice results in elevated levels of the pro-inflammatory cytokine interleukin-1β (IL-1β) and exacerbated neuropathology when compared to isolated-TBI. Here we examined the effect of treatment with an IL-1 receptor antagonist (IL-1ra) in mice given a TBI and a concomitant tibial fracture (i.e., polytrauma). Adult male C57BL/6 mice were given sham-injuries or polytrauma and treated with saline-vehicle or IL-1ra (100. mg/kg). Treatments were subcutaneously injected at 1, 6, and 24. h, and then once daily for one week post-injury. 7-8 mice/group were euthanized at 48. h post-injury. 12-16 mice/group underwent behavioral testing at 12. weeks post-injury and MRI at 14. weeks post-injury before being euthanized at 16. weeks post-injury. At 48. h post-injury, markers for activated microglia and astrocytes, as well as neutrophils and edema, were decreased in polytrauma mice treated with IL-1ra compared to polytrauma mice treated with vehicle. At 14. weeks post-injury, MRI analysis demonstrated that IL-1ra treatment after polytrauma reduced volumetric loss in the injured cortex and mitigated track-weighted MRI markers for axonal injury. As IL-1ra (Anakinra) is approved for human use, it may represent a promising therapy in polytrauma cases involving TBI and fracture.

Original languageEnglish
Pages (from-to)359-371
Number of pages13
JournalBrain, Behavior, and Immunity
Volume66
DOIs
Publication statusPublished - Nov 2017

Keywords

  • Fracture
  • IL-1β
  • MRI
  • Multitrauma
  • Neuroinflammation
  • Traumatic brain injury

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