Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines

Teeling, J.L., Felton, L.M., Deacon, R.M.J., Cunningham, C., Rawlins, J.N.P. and Perry, V.H. (2007) Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines. Brain, Behavior, and Immunity, 21, (6), 836-850. (doi:10.1016/j.bbi.2007.01.012).


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Systemic inflammation impacts on the brain and gives rise to behavioral changes, often referred to as ‘sickness behavior’. These symptoms are thought to be mainly mediated by pro-inflammatory cytokines. We have investigated the communication pathways between the immune system and brain following sub-pyrogenic inflammation. Low grade systemic inflammation was induced in mice using lipopolysaccharide (LPS); 1–100 ?g/kg to mimic aspects of bacterial infection. Changes in fever, open-field activity, burrowing and consumption of glucose solution were assessed and immune activation was studied in the periphery and brain by measuring cytokine production, and immunohistochemistry to study changes in immune cell phenotype. Sub-pyrogenic inflammation resulted in changes in a species-typical, untrained behavior (burrowing) that depends on the integrity of the hippocampus. Increased expression of cytokines was observed in the periphery and selected regions of the brain which coincided with changes in behavior. However, peripheral neutralization of LPS-induced pro-inflammatory cytokines IL-1?, IL-6 and TNF-? did not abrogate the LPS-induced behavioral changes nor affect CNS cytokine synthesis. In contrast, pretreatment of mice with indomethacin completely prevented LPS-induced behavior changes, without affecting cytokine levels. Taken together, these experiments suggest a key role for prostaglandins, rather than cytokines, in communicating to the brain.

Item Type: Article
Digital Object Identifier (DOI): doi:10.1016/j.bbi.2007.01.012
ISSNs: 0889-1591 (print)
Related URLs:
Keywords: cytokines, behavior, low grade sub-pyrogenic inflammation, prostaglandins
Subjects: R Medicine > RC Internal medicine > RC0321 Neuroscience. Biological psychiatry. Neuropsychiatry
Divisions : University Structure - Pre August 2011 > School of Biological Sciences
ePrint ID: 56381
Accepted Date and Publication Date:
August 2007Published
Date Deposited: 07 Aug 2008
Last Modified: 31 Mar 2016 12:36
Impact of systemic inflammation on cognition and the underlying mechanisms
Funded by: BBSRC (BBS/B/15864)
1 October 2004 to 31 January 2008

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