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Hepatic CC chemokines control the magnitude of the inflammatory response within the injured rodent brain

Hepatic CC chemokines control the magnitude of the inflammatory response within the injured rodent brain
Hepatic CC chemokines control the magnitude of the inflammatory response within the injured rodent brain
Hepatic CXC chemokines, behaving as acute phase proteins, regulate neutrophil mobilisation and recruitment following focal IL-1h-mediated inflammation to the rat brain. To determine whether this response was specific to CXC chemokines or whether it represented a more generalised response to acute brain inflammation, we examined brain and liver production of MCP-1, a CC chemokine, when rats were microinjected with TNF-a into the brain. As early as 2h after the TNF-a challenge, MCP-1 mRNA and protein were observed in the liver by Taqman RT-PCR and ELISA. The serum MCP-1 level was also elevated between 2 and 4 h, which was consistent with maximal mobilisation of leukocytes into the blood. Monocyte recruitment was most marked in the liver after 6 h, but was delayed in the brain until 24 h. Elevated hepaticand serum chemokines are implicated in the control of leukocytosis and leukocyte recruitment to the brain and liver, since dexamethasone pretreatment attenuated the hepatic MCP-1 response, modulated leukocyte mobilisation and reduced monocyte entry not only to the brain but also to the liver. Thus hepatic chemokine production controls and amplifies the CNS response to inflammation by controlling the rate, timing, magnitude and composition of leukocyte recruitment to the damaged brain.
0165-5728
33
Campbell, S.J.
fe349c31-dac5-42fb-ae2c-0f841b145083
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Pitossi, F.
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Butchart, A.G.
ba2335d5-425a-4f69-ae0b-aa57118ac5d9
Chertoff, M.
41d84d18-bc31-478a-bcfb-817cfd9370bd
Waters, S.
7eefd97d-ab0d-437b-8935-deee6b3a85f8
Anthony, D.C.
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Campbell, S.J.
fe349c31-dac5-42fb-ae2c-0f841b145083
Perry, V.H.
8f29d36a-8e1f-4082-8700-09483bbaeae4
Pitossi, F.
9f077ae6-4ca9-4cb5-8636-8da535e103f2
Butchart, A.G.
ba2335d5-425a-4f69-ae0b-aa57118ac5d9
Chertoff, M.
41d84d18-bc31-478a-bcfb-817cfd9370bd
Waters, S.
7eefd97d-ab0d-437b-8935-deee6b3a85f8
Anthony, D.C.
70fb8e27-4e74-4c72-b1b5-3a4ca0d6b8cf

Campbell, S.J., Perry, V.H., Pitossi, F., Butchart, A.G., Chertoff, M., Waters, S. and Anthony, D.C. (2004) Hepatic CC chemokines control the magnitude of the inflammatory response within the injured rodent brain. Journal of Neuroimmunology, 154 (1-2), 33. (doi:10.1016/j.jneuroim.2004.06.010).

Record type: Article

Abstract

Hepatic CXC chemokines, behaving as acute phase proteins, regulate neutrophil mobilisation and recruitment following focal IL-1h-mediated inflammation to the rat brain. To determine whether this response was specific to CXC chemokines or whether it represented a more generalised response to acute brain inflammation, we examined brain and liver production of MCP-1, a CC chemokine, when rats were microinjected with TNF-a into the brain. As early as 2h after the TNF-a challenge, MCP-1 mRNA and protein were observed in the liver by Taqman RT-PCR and ELISA. The serum MCP-1 level was also elevated between 2 and 4 h, which was consistent with maximal mobilisation of leukocytes into the blood. Monocyte recruitment was most marked in the liver after 6 h, but was delayed in the brain until 24 h. Elevated hepaticand serum chemokines are implicated in the control of leukocytosis and leukocyte recruitment to the brain and liver, since dexamethasone pretreatment attenuated the hepatic MCP-1 response, modulated leukocyte mobilisation and reduced monocyte entry not only to the brain but also to the liver. Thus hepatic chemokine production controls and amplifies the CNS response to inflammation by controlling the rate, timing, magnitude and composition of leukocyte recruitment to the damaged brain.

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Published date: September 2004

Identifiers

Local EPrints ID: 55904
URI: http://eprints.soton.ac.uk/id/eprint/55904
ISSN: 0165-5728
PURE UUID: 24f158f5-3401-470c-8844-a6cbe9590d70

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Date deposited: 06 Aug 2008
Last modified: 15 Mar 2024 10:58

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Contributors

Author: S.J. Campbell
Author: V.H. Perry
Author: F. Pitossi
Author: A.G. Butchart
Author: M. Chertoff
Author: S. Waters
Author: D.C. Anthony

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