Article

Role of cytokines and chemokines in prion infections of the central nervous system

Robert-Koch-Institute, Nordufer 20, 13353 Berlin, Germany.
International Journal of Developmental Neuroscience (Impact Factor: 2.92). 12/2004; 22(7):497-505. DOI: 10.1016/j.ijdevneu.2004.07.017
Source: PubMed

ABSTRACT Prion infections of the central nervous system (CNS) are characterised by a reactive gliosis and the subsequent degeneration of neuronal tissue. The activation of glial cells, which precedes neuronal death, is likely to be initially caused by the deposition of misfolded, proteinase K-resistant, isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glia cells may contribute directly or indirectly to the disease development by enhancement and generalisation of the gliosis and via cytotoxicity for neurons. However, the actual role of prion-induced glia activation and subsequent cytokine/chemokine secretion in disease development is still far from clear. In the present work, we review our present knowledge concerning the functional biology of cytokines and chemokines in prion infections of the CNS.

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    • "These changes are associated with the deposits of imperfectly folded proteinase K-resistant isoforms (termed PrP(res)) of the prion protein (PrP) in the brain. Cytokines and chemokines released by PrP(res)-activated glial cells may contribute directly or indirectly to development of the disease by enhancement and generalisation of the gliosis and via neuronal cytotoxicity (Eikelenboom et al., 2002; Burwinkel et al., 2004). Since the synthetic prion peptide PrP 106–126 shares many properties with PrP it is widely used for in vitro studies. "
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    • "), as those shown in Tables 4 and 6. Glial activation and the production of proinflammatory chemokines and cytokines have been shown to be associated with many central nervous system (CNS) diseases, such as bacterial or viral infection, multiple sclerosis, prion infection, Parkinson's disease, Alzheimer's disease and ischemia (Burwinkel et al., 2004; Choi et al., 2005; Meda et al., 2001). This association is in complete agreement with our findings that proinflammatory chemokines and cytokines are up-regulated and that the IFN-g signaling pathway may be activated by Mn 2+ in astrocytes. "
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