Sequential expression of chemokines in experimental autoimmune neuritis

Recruitment of inflammatory cells is of critical importance in the pathogen esis of immune-mediated demyelinating diseases in the peripheral nervous sy stem (PNS). Evidence is increasing that chemokines might play a key role in this process, since they promote leukocyte entry into the nervous system d uring immune-mediated inflammation. In the present study we report the expr ession pattern of the chemokines interferon-gamma -inducible protein (IP)-1 0, monocyte chemoattractant protein (MCP)-1, macrophage inflammatory protei n (MIP)-1 alpha, MIP-1 beta, and regulated upon activation normal T cell ex pressed and secreted (RANTES) in sciatic nerves from animals with myelin-in duced experimental autoimmune neuritis, using a semiquantitative reverse tr anscriptase-PCR dot-blot hybridization assay. The mRNAs for MIP-1 alpha and MIP-1 beta were found to be upregulated with peak values at day 13 post-im munization (p.i.), preceding maximum disease severity. In contrast, mRNAs f or MCP-1, RANTES, and IP-10 exhibited peak levels coincident with peak of t he disease at day 15 p.i. Increased mRNA expression was associated with enh anced protein levels, as demonstrated by immunoblotting for each chemokine investigated. Immunohistochemistry for IP-10 protein revealed immunoreactiv ity associated with perineurial endothelial cells. RANTES protein was local ized immunohistologically to invading T lymphocytes. Our findings suggest t hat chemokines, which act towards T cells and mononuclear phagocytes, are s equentially upregulated during the clinical course of EAN and thus may cont ribute to the pathogenesis of inflammatory demyelinating diseases of the PN S. (C) 2000 Elsevier Science B.V. All rights reserved.