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.