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

1:34 pm 15 Dec 2017

Available online 3 August 2017

Authors NIF

David K.Wright

This work was supported by grants to SRS from the National Health and Medical Research Council (grant number 1062653) and to SJM from La Trobe University (RFA Understanding Disease), as well as fellowships to SRS and BDS from NHMRC. We acknowledge the scientific and technical assistance of the animal MRI facility at the Florey Institute of Neuroscience and Mental Health, a node of the National Imaging Facility.

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.

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