Chemokines CXCL10 and CCL2: differential involvement in intrathecal inflammation in multiple sclerosis
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Chemokines CXCL10 and CCL2 : differential involvement in intrathecal inflammation in multiple sclerosis. / Sørensen, Torben Lykke; Sellebjerg, F; Jensen, C V; Strieter, R M; Ransohoff, R M.
In: European journal of neurology : the official journal of the European Federation of Neurological Societies, Vol. 8, No. 6, 11.2001, p. 665-72.Research output: Contribution to journal › Journal article › Research
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TY - JOUR
T1 - Chemokines CXCL10 and CCL2
T2 - differential involvement in intrathecal inflammation in multiple sclerosis
AU - Sørensen, Torben Lykke
AU - Sellebjerg, F
AU - Jensen, C V
AU - Strieter, R M
AU - Ransohoff, R M
PY - 2001/11
Y1 - 2001/11
N2 - Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation.
AB - Studies of chemokines in cerebrospinal fluid (CSF) of patients with active multiple sclerosis (MS) have indicated that specific chemokines may have important roles in disease pathogenesis. We previously reported that CSF concentrations of CXCL10 (previously known as IP-10) were elevated in MS patients in relapse, whilst levels of CCL2 (MCP-1) were reduced. Here, we report a serial analysis of CSF CXCL10 and CCL2 concentrations in 22 patients with attacks of MS or acute optic neuritis (ON) treated with methylprednisolone, and 26 patients treated with placebo in two randomized controlled trials. Chemokine concentrations were measured by enzyme linked immunosorbent assay (ELISA) in CSF obtained at baseline and after 3 weeks, and were compared with other measures of intrathecal inflammation. At baseline CSF concentrations of CCL2 were significantly lower in the patient group than in controls. The levels of CXCL10 were higher in the patient group than in controls but two outliers in the control group also had high CSF concentrations of CXCL10. The CSF concentrations of CXCL10 did not change over time or after treatment. The CSF concentration of CXCL10 was positively correlated with the CSF leukocyte count, the CSF concentration of neopterin, matrix metalloproteinase (MMP)-9, and intrathecal IgG and IgM synthesis. The concentration of CCL2 increased between baseline for 3 weeks in both groups, more distinctly so in patients treated with methylprednisolone. CCL2 correlated negatively with MMP-9 and IgG synthesis levels. CXCL10 may be involved in the maintenance of intrathecal inflammation whereas CCL2 correlates negatively with measures of inflammation, suggesting differential involvement of CXCL10 and CCL2 in CNS inflammation.
KW - Anti-Inflammatory Agents
KW - Chemokine CCL2
KW - Chemokine CXCL10
KW - Chemokines, CXC
KW - Humans
KW - Immunoglobulin G
KW - Immunoglobulin M
KW - Magnetic Resonance Imaging
KW - Matrix Metalloproteinase 9
KW - Methylprednisolone
KW - Multiple Sclerosis
KW - Neopterin
M3 - Journal article
C2 - 11784351
VL - 8
SP - 665
EP - 672
JO - European Journal of Neurology
JF - European Journal of Neurology
SN - 1351-5101
IS - 6
ER -
ID: 111410662