To investigate associations of C-C motif Ligand 18 (CCL18), C-C motif ligand 5 (CCL5) and soluble Cluster of Differentiation 86 (sCD86) with clinical and MRI measures in MS patients.
These data suggest that mutation of the RANTES allele can predispose to the induction of demyelination similarly to what has been observed in Multiple Sclerosis (MS) and may suggest a possible explanation for the development of leukoencephalopathy without detection of JCV.
This observation supports the hypothesis that in MS, chemokine CCL5 may induce migration of leukocytes to the CNS and suggests that treatment of the disease with MP and MTX may reduce this migration.
RANTES is a basic 8-kDa polypeptide of the C-C chemokine subfamily with strong chemoattractant activity for T lymphocytes and monocytes/macrophages that are implicated in the pathogenesis of multiple sclerosis (MS) lesions.
Although analysis of cytokine and cytokine receptor genes expression showed predominantly increased levels of several Th1 molecules (TGF-ss, RANTES, and macrophage-inflammatory protein (MIP)-1alpha) in MS samples, some Th2 genes (IL-3, IL-5, and IL-6/IL-6R) were found to be up-regulated as well.
The method could detect and quantitate RANTES in small amounts of brain tissue from all patients with multiple sclerosis, and in some patients with other neural or inflammatory diseases.
In actively demyelinating MS plaques RANTES expression was restricted to the blood vessel endothelium, perivascular cells and surrounding astrocytes, suggesting a role in the recruitment of inflammatory cells from the circulation.
This shows that elevated numbers of MCP-1 and RANTES mRNA expressing CSF MNC are not specific for the inflammatory process in MS. We conclude that there is no evidence for a systemic dysregulation of the CC chemokines MCP-1 and RANTES in MS.
In view of the regulatory and chemotactic properties of RANTES, these results imply that RANTES in MS lesions may play an important role in the activation and/or selective accumulation of memory T cells and, thereby, in the pathogenic events associated with MS.