Requirement for interleukin-1 to drive brain inflammation reveals tissue-specific mechanisms of innate immunity
Open Access
- 4 November 2014
- journal article
- research article
- Published by Wiley in European Journal of Immunology
- Vol. 45 (2), 525-530
- https://doi.org/10.1002/eji.201444748
Abstract
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.Keywords
Funding Information
- Medical Research Council (MR/L003384/1)
- Biotechnology and Biological Sciences Research Council (BB/J004332/1)
- Biotechnology and Biological Sciences Research Council (BB/J004243/1)
- Biotechnology and Biological Sciences Research Council (BB/J004332/1)
- Medical Research Council (MR/K001744/1)
- Natural Environment Research Council (R8/H10/56)
- Darwin Trust of Edinburgh
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