Chemokines in the cerebrospinal fluid of patients with active and stable relapsing-remitting multiple sclerosis

M.A Moreira,A.L.S Souza,M.A Lana-Peixoto,M.M Teixeira,A.L Teixeira

doi:10.1590/s0100-879x2006000400003

Abstract

Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the human central nervous system. Although its etiology is unknown, the accumulation and activation of mononuclear cells in the central nervous system are crucial to its pathogenesis. Chemokines have been proposed to play a major role in the recruitment and activation of leukocytes in inflammatory sites. They are divided into subfamilies on the basis of the location of conserved cysteine residues. We determined the levels of some CC and CXC chemokines in the cerebrospinal fluid (CSF) of 23 relapsing-remitting MS patients under interferon-ss-1a therapy and 16 control subjects using ELISA. MS patients were categorized as having active or stable disease. CXCL10 was significantly increased in the CSF of active MS patients (mean +/- SEM, 369.5 +/- 69.3 pg/mL) when compared with controls (178.5 +/- 29.1 pg/mL, P < 0.05). CSF levels of CCL2 were significantly lower in active MS (144.7 +/- 14.4 pg/mL) than in controls (237.1 +/- 16.4 pg/mL, P < 0.01). There was no difference in the concentration of CCL2 and CXCL10 between patients with stable MS and controls. CCL5 was not detectable in the CSF of most patients or controls. The qualitative and quantitative differences of chemokines in CSF during relapses of MS suggest that they may be useful as a marker of disease activity and of the mechanisms involved in the pathogenesis of the disease.

Highlights

Multiple sclerosis (MS) is a chronic inflammatory disease of the human central nervous system (CNS) resulting in the formation of plaques of demyelination
Previous studies have demonstrated that in MS CXCL10 and CCL5 are increased in the cerebrospinal fluid (CSF) of patients with MS compared with control subjects, while CCL2 is significantly decreased [7,8,9,10]
We evaluated CSF levels of CXCL10, CCL2 and CCL5 in active relapsing-remitting MS (RR-MS) and stable RR-MS patients and in individuals with no neurological disorders

Summary

Introduction

Multiple sclerosis (MS) is a chronic inflammatory disease of the human central nervous system (CNS) resulting in the formation of plaques of demyelination. The cause of MS is unknown, it is generally considered to be an autoimmune disease mediated by CD4+ T cells, which produce high levels of type 1 cytokines, such as interferon-γ [1,2]. These Th1 cells initiate an inflammatory process, recruiting and activating circulatory monocytes as well as microglia cells, which destroy myelin. Since mononuclear cell recruitment and activation in the CNS are fundamental steps in the pathogenesis of MS, chemokines have been proposed to play a major role in this autoimmune demyelinating process [7]. There is a growing body of evidence suggesting that these altered CSF chemokine levels could be used as surrogate markers of MS disease activity [9]

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Conclusion