J Neurosci Res 2002 Mar 1;67(5):680-8
Matejuk A, Dwyer J, Ito A, Bruender Z, Vandenbark AA, Offner H.
Department of Neurology, Oregon Health and Science University, Portland, Oregon.
Although both cytokines and chemokines have been implicated in the pathogenesis of clinical and histological EAE, their interactions in vivo have not yet been clearly established.
To address this issue, we evaluated expression of chemokines and receptors in the CNS of wild-type control and cytokine deficient mice at the peak of EAE induced with MOG-35-55 peptide in CFA.
Our results demonstrate that:
1) expression of most chemokines/receptors was drastically inhibited in TNF-alpha deficient mice, and was reflective of delayed onset and reduced severity of EAE;
2) distinct patterns of chemokine expression occurred in various other cytokine knockout mice that did not significantly affect expression of clinical EAE;
3) there was a strong association between expression of MIP-1alpha, MIP-2 and MCP-1 in CNS and overall severity of EAE in wild-type and cytokine knockout mice; and 4) among CNS infiltrating cells at the peak of EAE, macrophages and CD8+ T cells were the primary cellular source of most of the chemokines.
Of note, we present evidence that TNF-alpha may be involved in regulating RANTES and MIP-1alpha, and that IL-4 may be involved in regulating MCP-1.
Our results not only identify the cellular source of chemokines in CNS, but also implicate MIP-1alpha, MIP-2, and MCP-1 in controlling CNS inflammation and severity of EAE.
Copyright 2002 Wiley-Liss, Inc.