Sickness behaviour is induced by a peripheral CXC-chemokine also expressed in Multiple Sclerosis and EAE |
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| Authors: | Sandra J. Campbell Ute Meier Silvy Mardiguian Yanyan Jiang Edward T. Littleton Adrian Bristow Jane Relton Thomas J. Connor Daniel C. Anthony |
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| Affiliation: | 1. Experimental Neuropathology, Department of Pharmacology, University of Oxford, Oxford, OX1 3QT, UK;2. Neuroscience Centre, Barts and The London School of Medicine and Dentistry, 4 Newark Street, London E1 2AT, UK;3. National Institute of Biological Standard and Controls (NISBC), Blanche Lane, South Mimms, Potters Bar, Hertfordshire, EN6 3QG, UK;4. School of Medicine & Trinity College Institute of Neuroscience, Trinity College, Dublin 2, Ireland;5. Department of Clinical Neurology, John Radcliffe Hospital, Oxford, OX3 9DU, UK;6. Biogen IDEC, 14 Cambridge Centre, Cambridge, MA 02142, USA;1. Departamento de Análises Clínicas, Toxicológicas e Bromatológicas, Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil;2. Departamento de Química, Universidade Federal de São Carlos, São Carlos, SP, Brazil;3. Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Ribeirão Preto, SP, Brazil;1. Centre for Biological Sciences, Faculty of Natural and Environmental Sciences, Building 85, University of Southampton, Southampton SO17 1BJ, UK;2. Centre for Biological Sciences, Mailpoint 840 (room LD80b), Level D Laboratories and Pathology Block, Southampton General Hospital, Tremona Road, Southampton SO16 6YD, UK;3. Peninsula School of Medicine and Dentistry, University of Plymouth, Devon, PL4 8AA, UK;1. Department of Oral and Maxillofacial Surgery, Shimane University Faculty of Medicine, Izumo, Japan;2. Department of Developmental Biology, Shimane University Faculty of Medicine, Izumo, Japan |
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| Abstract: | Non-CNS chemokine production may contribute to previously unrecognised components of Multiple Sclerosis (MS) pathology. Here we show that IL-8, a neutrophil chemoattractant, is significantly increased in serum from individuals with MS, and that the rodent homolog of IL-8 (CXCL1) is expressed in the liver in experimental autoimmune encephalomyelitis (EAE), a rodent model of MS. The hepatic expression of CXCL1 in EAE is accompanied by neutrophil recruitment to the liver, and we show that this recruitment is a feature of post mortem liver tissue from MS patients, which is a previously unrecognised phenomenon. We speculated that the presence of peripheral CXC-chemokine expression might contribute to the sickness behaviours associated with MS, which are a significant contributor to morbidity. Peripheral, but not central, administration of CXCL1 to Wistar rats inhibited spontaneous activity in the open field and burrowing behaviour in a dose-dependent manner (5–45 μg). The expression of CXCL1 by the liver and the recruitment of neutrophils can be modelled by the intracerebral injection of IL-1β. Here, we found that interferon-beta (IFN-β) pretreatment significantly inhibited hepatic CXCL1 production and neutrophil recruitment to the liver induced by the microinjection of IL-1β into the brain. Thus while the mechanism by which IFN-β therapy suppresses disease in MS remains unclear, the data presented here suggests that the inhibition of hepatic chemokine synthesis may be a contributing factor. |
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