Expression of leukemia inhibitory factor in the cerebrospinal fluid of patients with multiple sclerosis

Abstract

Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system, characterized by infiltration of immune cells in the central nervous system, localized myelin destruction and loss of oligodendrocytes. Early detection of MS may be possible via blood and cerebrospinal fluid (CSF) tests based on disease pathology. Leukemia inhibitory factor (LIF), a neurotrophic cytokine, has previously been shown to limit autoimmune demyelination and oligodendrocyte loss in a murine model of MS. Given its potential role in neural cell death and survival, in the present study we measured expression of LIF in serum and CSF from patients with relapsing-remitting MS ( n = 46) and control subjects ( n = 42). We used western blot analysis and enzyme-linked immunosorbent assays (ELISA), to study LIF expression. Western blot analysis revealed that LIF was present in all CSF samples, and densitometric analysis showed that relative expression was significantly higher in CSF from patients with MS than in controls ( p < 0.001). ELISA analysis showed that the concentrations of LIF in both the serum (87.5 ± 11.46 ng/mL) and CSF (56 ± 10.72 ng/mL) of MS patients were significantly higher than those in control subjects (52 ± 8.23 ng/mL, 7.8 ± 3.76 ng/mL, respectively; p < 0.0001 for both serum and CSF), despite there being no significant difference in total protein concentration between the two groups ( p = 0.52 for serum, p = 0.2 for CSF). Our data suggest that serum and CSF concentrations of LIF may provide additional useful information during the differential diagnosis of MS. Our findings also indicate that LIF could be significantly involved in the pathophysiology of MS.