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

SANDRA J. CAMPBELL,; V. HUGH PERRY,; PITOSSI F; ANGUS G. BUTCHART,; MARIELA CHERTOFF; SARA WATERS; DANIEL C. ANTHONY

Italia

Congreso; International Society of Neuroimmunology, 7th International Congress; 2004

INTERNATIONAL SOCIETY OF NEUROIMMUNOLOGY

Hepatic CXC chemokines, behaving as acute phase proteins, regulate neutrophil mobilisation and recruitment following focal IL-1 beta-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 brainand liver production of MCP-1, a CC chemokine, when rats were microinjected with TNF-alpha into the brain. As early as 2h after the TNF-alpha challenge, MCP-1 mRNA and protein were observed in the liver by Taqman RT-PCR and ELISA. The serum MCP-a 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 theliver after 6 h, but was delayed in the brain until 24 h. Elevated hepatic and serum chemokines are implicated in the control of leukocytosis and leukocyte recruitment to the brain and liver, since dexamethasone pretreatment attenuated the hepatic MCP-l response, modulated leukocyte mobilisation and reduced monocyte entry not only to the brain but also to the liver. Thus hepatic chemokine production controls and amplifiesthe CNS response to inflammation by controlling the rate, timing, magnitude and composition of leukocyte recruitment to the damaged brain.