Inflammation occurs rapidly in response to acute brain insults such as stroke, haemorrhage or trauma, and can be sustained for long periods of time, for example in Alzheimer's or Parkinson's diseases and multiple sclerosis. Experimental evidence indicates that inflammation plays a major role in neurodegeneration under these conditions, and that the cytokine IL-1 (interleukin-1) is a pivotal mediator. IL-1 is expressed rapidly in response to neuronal injury, predominantly by microglia, and elevated levels of endogenous or exogenous IL-1 markedly exacerbate injury. The naturally occurring IL-1RA (IL-1 receptor antagonist) markedly inhibits ischaemic, excitotoxic and traumatic brain injury in rodents, and has shown promise in a Phase II clinical trial in stroke patients. The mechanisms of IL-1 expression, release and action in neurodegeneration are not fully elucidated and appear multiple. Systemic IL-1 markedly enhances ischaemic brain injury via release of neutrophils into circulation, neutrophil adhesion to injured cerebrovasculature and CNS (central nervous system) invasion, and cell death via activation of matrix metalloproteinase-9. IL-1 also influences the release of toxins from glial and endothelial cells. Neuronal responses to excitotoxins and physiological factors may have an impact on neuronal survival. IL-1RA, delivered peripherally, can enter the CNS in animals and humans and has no adverse effects in stroke or subarachnoid haemorrhage patients, but shows potential benefit in acute stroke patients.
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November 2007
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Conference Article|
October 25 2007
Interleukin-1 and inflammatory neurodegeneration
A. Simi;
A. Simi
*Department of Neuroscience, Division of Molecular Neurobiology, Karolinska Institutet, S-171 77 Stockholm, Sweden
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N. Tsakiri;
N. Tsakiri
†Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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P. Wang;
P. Wang
†Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
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N.J. Rothwell
N.J. Rothwell
1
†Faculty of Life Sciences, University of Manchester, Manchester M13 9PT, U.K.
1To whom correspondence should be addressed (email nancy.rothwell@manchester.ac.uk).
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Publisher: Portland Press Ltd
Received:
June 07 2007
Online ISSN: 1470-8752
Print ISSN: 0300-5127
© The Authors Journal compilation © 2007 Biochemical Society
2007
Biochem Soc Trans (2007) 35 (5): 1122–1126.
Article history
Received:
June 07 2007
Citation
A. Simi, N. Tsakiri, P. Wang, N.J. Rothwell; Interleukin-1 and inflammatory neurodegeneration. Biochem Soc Trans 1 November 2007; 35 (5): 1122–1126. doi: https://doi.org/10.1042/BST0351122
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