Cerebrospinal Hepatocyte Growth Factor Levels Correlate Negatively with Disease Activity in Multiple Sclerosis

The hepatocyte growth factor (HGF) is a pleiotropic cytokine with neuroprotective and anti-inflammatory properties. Additionally, it enhances axonal outgrowth and oligodendroglial maturation. We studied the expression of HGF by cells derived from cerebrospinal fluid (CSF), quantified HGF in CSF samples and investigated the glial expression of HGF in vitro. We found decreased expression of HGF in CSF cells as well as reduced CSF but not plasma HGF protein levels in MS. MS patients with active disease had lower HGF CSF levels than inactive MS patients, and treatment with Natalizumab correlated with increased CSF concentration of HGF. In vitro, glial production of HGF was reduced by CSF from MS patients in comparison with CSF from controls. CSF levels of CCL2, a known inducer of HGF, also correlated strongly with HGF levels. We conclude that the expression of HGF within the CNS is reflective of disease activity in MS and this may be due to decreased induction of HGF by CCL2. Furthermore, the decreased HGF associated with active disease may potentially contribute to reduced stimulation for remyelination and the occurrence of shadow plaques frequently seen in MS patients. Our results merit further validation to establish whether CSF HGF is a biomarker for MS disease activity.