The role of inflammation in CNS injury and disease

[Guest guest]

British Journal of Pharmacology (2006) 147, S232–S240.

doi:10.1038/sj.bjp.0706400

The role of inflammation in CNS injury and disease

Sian-Marie Lucas1, J Rothwell1 and Rosemary M Gibson1,2

1Faculty of Life Sciences, Building, University of Manchester,

Oxford Road, Manchester M13 9PT

Correspondence: J. Rothwell, E-mail: .Rothwell@...

2Current 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.

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http://www.nature.com/bjp/journal/v147/n1s/full/0706400a.html