The role of inflammation in CNS injury and disease.
Journal: 2006/December - British Journal of Pharmacology
ISSN: 0007-1188
Abstract:
For many years, the central nervous system (CNS) was considered to be 'immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.
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Br J Pharmacol 147(Suppl 1): S232-S240

The role of inflammation in CNS injury and disease

Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT
Faculty of Life Sciences, Michael Smith Building, University of Manchester, Oxford Road, Manchester M13 9PT. E-mail: ku.ca.retsehcnam@llewhtoR.ycnaN
Current address: Health & Safety Laboratory, Harpur Hill, Buxton, SK17 9JN.

Abstract

For many years, the central nervous system (CNS) was considered to be ‘immune privileged', neither susceptible to nor contributing to inflammation. It is now appreciated that the CNS does exhibit features of inflammation, and in response to injury, infection or disease, resident CNS cells generate inflammatory mediators, including proinflammatory cytokines, prostaglandins, free radicals and complement, which in turn induce chemokines and adhesion molecules, recruit immune cells, and activate glial cells. Much of the key evidence demonstrating that inflammation and inflammatory mediators contribute to acute, chronic and psychiatric CNS disorders is summarised in this review. However, inflammatory mediators may have dual roles, with detrimental acute effects but beneficial effects in long-term repair and recovery, leading to complications in their application as novel therapies. These may be avoided in acute diseases in which treatment administration might be relatively short-term. Targeting interleukin (IL)-1 is a promising novel therapy for stroke and traumatic brain injury, the naturally occurring antagonist (IL-1ra) being well tolerated by rheumatoid arthritis patients. Chronic disorders represent a greater therapeutic challenge, a problem highlighted in Alzheimer's disease (AD); significant data suggested that anti-inflammatory agents might reduce the probability of developing AD, or slow its progression, but prospective clinical trials of nonsteroidal anti-inflammatory drugs or cyclooxygenase inhibitors have been disappointing. The complex interplay between inflammatory mediators, ageing, genetic background, and environmental factors may ultimately regulate the outcome of acute CNS injury and progression of chronic neurodegeneration, and be critical for development of effective therapies for CNS diseases.

Keywords: Cytokine, neurodegeneration, COX, NO, interleukin, tumour necrosis factor, complement
Abstract

Glossary

Aβamyloid β
ADAlzheimer's disease
ALSamyotropic lateral sclerosis
BBBblood--brain barrier
CJDCreutzfeldt–Jakob disease
CNScentral nervous system
COXcyclooxygenase
CSFcerebral spinal fluid
GABAγ-amino butyric acid
IFNinterferon
ILinterleukin
IL-1Rinterleukin-1 receptor
IL-1rainterleukin-1 receptor antagonist
IL-6Rinterleukin-6 receptor
iNOSinducible nitric oxide synthase
L-NMMAN(omega)-monomethyl-L-arginine
MACmembrane attack complex
MHCmajor histocompatability complex
MPTP1-methyl-4-phenyl-l,2,3,6-tetrahydropyridine
MSmultiple sclerosis
NMDAN-methyl-D-aspartate
NOnitric oxide
NSAIDnonsteroidal anti-inflammatory drug
PDParkinson's disease
PGprostaglandin
SODsuperoxide dismutase
TACETNFα-converting enzyme
TBItraumatic brain injury
TNFtumour necrosis factor
Glossary
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