Expression of chemokines in the CSF and correlation with clinical disease activity in patients with multiple sclerosis.
OBJECTIVE
To define the chemokine profile in the CSF of patients with multiple sclerosis (MS) and compare it with three control groups; patients with benign headache (headache), non-inflammatory neurological diseases (NIND), and other inflammatory neurological diseases (IND). In addition, the correlations of CSF chemokine concentrations with chemokine receptor expression on CSF CD4(+) T cells and with clinical disease activity were assessed.


METHODS
Forty three patients with MS, 24 with IND, 44 with NIND, and 12 with benign headache undergoing diagnostic or therapeutic lumbar puncture were included. Supernatant fluid from CSF was analysed for four beta (CCL2, CCL3, CCL4, CCL5) and two alpha (CXCL9, CXCL10)chemokines by enzyme linked immunosorbent assay (ELISA). Chemokine receptors CCR3, CCR5, and CXCR3 on CD4(+) T cells from eight patients with MS were analysed using directly conjugated fluorescent labelled monoclonal antibodies and flow cytometry.


RESULTS
CXCL10, formerly interferon-gamma inducible protein-10 (IP-10), was significantly increased and CCL2, formerly monocyte chemoattractant protein-1 (MCP-1), was significantly reduced in the CSF of patients with MS and IND compared with those with benign headache and NIND. Concentrations of CXCL10 were significantly greater in patients with relapsing-remitting compared with secondary progressive MS and correlated significantly with CXCR3 expression on CSF CD4(+) T cells from patients with MS. Concentrations of CXCL10 decreased and CCL2 concentrations increased as time from the last relapse increased in patients with MS.


CONCLUSIONS
Increased CXCL10 and decreased CCL2 concentrations in the CSF are associated with relapses in MS. Although serial values from individual patients were not available, this study suggests that CXCL10 and CCL2 may return towards baseline concentrations after a relapse. Correlation of CXCL10 with CD4(+) T cell expression of CXCR3 was consistent with its chemoattractant role for activated lymphocytes. Thus CXCL10 neutralising agents and CXCR3 receptor antagonists may be therapeutic targets in MS.
Mahad
D J
DJ
Division of Biomedical Sciences, Sheffield Hallam University, Howard Street, Sheffield S1 1WB, UK. D.J.Mahad@shu.ac.uk
Howell
S J L
SJ
Woodroofe
M N
MN
D000328:Adult; D015415:Biomarkers / Q000032:analysis*; D018925:Chemokines / Q000134:cerebrospinal fluid*; D018450:Disease Progression; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005434:Flow Cytometry; D006261:Headache / Q000503:physiopathology; D006801:Humans; D008297:Male; D009103:Multiple Sclerosis / Q000503:physiopathology*; D019707:Receptors, Chemokine / Q000096:biosynthesis; D012008:Recurrence
D015415:Biomarkers; D018925:Chemokines; D019707:Receptors, Chemokine