Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity.

James A Giles, Andrew D Greenhalgh, Claire L Davies, Adam Denes, Tovah Shaw, Graham Coutts, Nancy J Rothwell, Barry W McColl, Stuart M Allan

Research output: Contribution to journalArticlepeer-review


The immune system is implicated in a wide range of disorders affecting the brain and is, therefore, an attractive target for therapy. Interleukin-1 (IL-1) is a potent regulator of the innate immune system important for host defense but is also associated with injury and disease in the brain. Here, we show that IL-1 is a key mediator driving an innate immune response to inflammatory challenge in the mouse brain but is dispensable in extracerebral tissues including the lung and peritoneum. We also demonstrate that IL-1α is an important ligand contributing to the CNS dependence on IL-1 and that IL-1 derived from the CNS compartment (most likely microglia) is the major source driving this effect. These data reveal previously unknown tissue-specific requirements for IL-1 in driving innate immunity and suggest that IL-1-mediated inflammation in the brain could be selectively targeted without compromising systemic innate immune responses that are important for resistance to infection. This property could be exploited to mitigate injury- and disease-associated inflammation in the brain without increasing susceptibility to systemic infection, an important complication in several neurological disorders.
Original languageEnglish
JournalEuropean journal of immunology
Publication statusPublished - 4 Nov 2014


  • innate immunity
  • interleukin-1 (IL-1)
  • neuroinflammation
  • neutrophil


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