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

Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines
Sub-pyrogenic systemic inflammation impacts on brain and behavior, independent of cytokines
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.
cytokines, behavior, low grade sub-pyrogenic inflammation, prostaglandins
0889-1591
836-850
Teeling, J.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Felton, L.M.
74fbd391-ce55-44aa-b297-499dccc644f1
Deacon, R.M.J.
db1b08cb-3bd1-41b4-b665-c8435b753019
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Rawlins, J.N.P.
73d67088-43cc-4727-8af3-7195f3ed9f85
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Teeling, J.L.
fcde1c8e-e5f8-4747-9f3a-6bdb5cd87d0a
Felton, L.M.
74fbd391-ce55-44aa-b297-499dccc644f1
Deacon, R.M.J.
db1b08cb-3bd1-41b4-b665-c8435b753019
Cunningham, C.
6d675038-a4b1-46e2-9e4b-0a5ac27ea2b2
Rawlins, J.N.P.
73d67088-43cc-4727-8af3-7195f3ed9f85
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4

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).

Record type: Article

Abstract

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.

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More information

Published date: August 2007
Keywords: cytokines, behavior, low grade sub-pyrogenic inflammation, prostaglandins

Identifiers

Local EPrints ID: 56381
URI: http://eprints.soton.ac.uk/id/eprint/56381
ISSN: 0889-1591
PURE UUID: 6b0b537d-b027-414f-a574-158a9afcf302
ORCID for J.L. Teeling: ORCID iD orcid.org/0000-0003-4004-7391

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Date deposited: 07 Aug 2008
Last modified: 16 Mar 2024 03:41

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Contributors

Author: J.L. Teeling ORCID iD
Author: L.M. Felton
Author: R.M.J. Deacon
Author: C. Cunningham
Author: J.N.P. Rawlins
Author: V.H. Perry

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