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

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 (100mg/kg). Treatments were subcutaneously injected at 1, 6, and 24h, and then once daily for one week post-injury. 7-8 mice/group were euthanized at 48h post-injury. 12-16 mice/group underwent behavioral testing at 12weeks post-injury and MRI at 14weeks post-injury before being euthanized at 16weeks post-injury. At 48h 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 14weeks 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.

• Authors: Mujun Sun, Rhys D Brady, David K Wright, Hyun Ah Kim, Shenpeng R Zhang, Christopher G Sobey, Maddison R Johnstone, Terence J O'Brien, Bridgette D Semple, Stuart J McDonald, Sandy R Shultz
• Journal: Brain, behavior, and immunity (Brain Behav Immun) Vol. 66 Pg. 359-371 (Nov 2017) ISSN: 1090-2139 [Electronic] Netherlands
• PMID: 28782716 (Publication Type: Journal Article)
• Copyright: Crown Copyright © 2017. Published by Elsevier Inc. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Interleukin 1 Receptor Antagonist Protein

Topics

• Animals
• Anti-Inflammatory Agents (administration & dosage)
• Atrophy (complications)
• Behavior, Animal
• Brain Edema (complications)
• Brain Injuries, Traumatic (complications)
• Cerebral Cortex (drug effects, pathology, physiopathology)
• Encephalitis (drug therapy, etiology, metabolism)
• Interleukin 1 Receptor Antagonist Protein (administration & dosage)
• Macrophages (drug effects, metabolism)
• Male
• Mice, Inbred C57BL
• Microglia (drug effects, metabolism)
• Multiple Trauma (complications)
• Tibial Fractures (complications)