Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration

Palin, Karine, Cunningham, Colm, Forse, Penny, Perry, V. Hugh and Platt, Nick (2008) Systemic inflammation switches the inflammatory cytokine profile in CNS Wallerian degeneration. Neurobiology of Disease, 30, (1), 19-29. (doi:10.1016/j.nbd.2007.11.012). (PMID:18255301).


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Axon loss in the CNS is characteristic of many neurodegenerative diseases but the mechanisms of axon degeneration are poorly understood. In particular, we know little of the inflammatory response triggered by CNS axon degeneration with comparison to that provoked by death of the neuronal cell body. We show that Wallerian degeneration of the mouse optic nerve induces transcription of TGF-?1 and TNF-?, but not pro-inflammatory cytokines IL-1? and IL-6 and microglial activation. This atypical inflammatory response resembles macrophages that have phagocytosed apoptotic cells and prion-infected CNS. Significantly, peripheral endotoxin challenge after injury switched this profile by inducing IL-1?, IL-6 transcripts, other inflammation-associated products and reducing neurofilament immunoreactivity. We propose that microglia are activated by Wallerian degeneration and persist in an atypical but “primed” state and can be switched by systemic inflammation to provoke a classical pro-inflammatory profile with potentially deleterious consequences.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.nbd.2007.11.012
ISSNs: 0969-9961 (print)
1095-953X (electronic)
Keywords: axon, neurodegeneration, microglia, lipopolysaccharide
Subjects: Q Science > Q Science (General)
Q Science > QR Microbiology
Divisions : University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 56030
Accepted Date and Publication Date:
April 2008Published
23 December 2007Made publicly available
Date Deposited: 21 Aug 2008
Last Modified: 31 Mar 2016 12:36

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