Neuronal injury induces the release of pro-interleukin-1β from activated microglia in vitro

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Microglia activated after brain injury, are a major source of the pro-inflammatory cytokine interleukin-1 (IL-1), which is known to further exacerbate damage. However, the mechanisms that control IL-1 release in acute neuronal injury are unknown and the purpose of this study was to test the hypothesis that neuronal injury induces IL-1β release from microglial cells. Here we report that lipopolysaccharide (LPS)-activated rat microglia co-cultured with healthy rat neurons express pro-IL-1β, which in the absence of cell death accumulates in the cells. Treatment of co-cultures with the excitotoxin N-methyl-d-aspartate (NMDA) induced neuronal cell death leading to the appearance of pro-IL-1β in the culture supernatant. This effect was reversed by the NMDA receptor antagonist MK-801, and was neuron-dependent, since NMDA had no effect on cell death or pro-IL-1β release in mixed glial cell cultures. In addition, we show that pro-IL-1β release from LPS-treated mixed glia or LPS-treated microglia is significantly reduced in the presence of conditioned medium from healthy co-cultures or neuronal cultures respectively. These results demonstrate that injured neurons promote the release of pro-IL-1β from microglia, possibly by regulating microglial cell viability, and suggest an important alternative mechanism of IL-1β release that occurs in response to neuronal injury. © 2008 Elsevier B.V. All rights reserved.
Original languageEnglish
Pages (from-to)1-7
Number of pages6
JournalBrain research
Publication statusPublished - 21 Oct 2008


  • Cell death
  • Cytokine release
  • Interleukin-1
  • Microglia
  • Neuron

Research Beacons, Institutes and Platforms

  • Dementia@Manchester


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