Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis

Giuseppe Scalabrino, Daniela Galimberti, Elena Mutti, Diego Scalabrini, Daniela Veber, Milena De Riz, Fabrizia Bamonti, Elisabetta Capello, Giovanni Luigi Mancardi, Elio Scarpini

Research output: Contribution to journalArticlepeer-review


We investigated whether the physiological regulation of cerebrospinal fluid (CSF) levels of tumor necrosis factor (TNF)-α, epidermal growth factor (EGF), and nerve growth factor (NGF) by cobalamin (Cbl) that is observed in rat and human central nervous system (CNS) is retained in the CSF of patients with multiple sclerosis (MS). The study involved 158 MS patients grouped on the basis of the different clinical courses (relapsing-remitting (RR), secondary-progressive (SP), and primary-progressive (PP)), and 76 gender- and age-matched control patients with other non-inflammatory and non-neoplastic neurological diseases. The MS patients were therapy-free at the time of lumbar puncture. CSF Cbl and EGF were blindly measured by means of radioimmunoassays, and CSF TNF-α, and NGF by means of highly sensitive enzyme-linked immunosorbent assays. Serum EGF was also measured in 38 of the MS patients and 20 healthy controls. CSF Cbl levels were significantly higher (RR patients 27.9 ± 9.7 pg/ml, p <0.0001 vs. C; SP patients 25.4 ± 8 pg/ml, p <0.02 vs. C), and CSF TNF-α and EGF levels significantly lower in the patients with the RR (TNF-α 28.3 ± 23.4 × 10 -3 pg/ml, p <0.0001 vs. C; EGF 129.9 ± 44.8 pg/ml, p <0.02 vs. C) or SP (TNF-α 20.5 ± 20.5 × 10 -3 pg/ml, p <0.001 vs. C; EGF 116.5 ± 24.8 pg/ml, p <0.05 vs. C) clinical course than in controls (Cbl 21 ± 4.6 pg/ml; TNF-α 75.6 ± 34.7 × 10 -3 pg/ml; EGF 170.2 ± 54.8 pg/ml). There were no differences in CSF NGF or serum EGF levels between any of the MS clinical courses and controls. Our results indicate that: (a) the positive Cbl-mediated regulation of myelino- and oligodendrocyte-trophic EGF is lost in the CSF of RR- or SP-MS patients; (b) the decrease in EGF levels in the CSF may be one factor impeding CNS remyelination in MS; and (c) the PP clinical course may have different pathogenetic mechanism(s) also on the basis of the molecules investigated in this study.

Original languageEnglish
Pages (from-to)64-71
Number of pages8
JournalBrain Research
Publication statusPublished - May 28 2010


  • Cerebrospinal fluid
  • Cobalamin
  • Epidermal growth factor
  • Multiple sclerosis
  • Nerve growth factor
  • Tumor necrosis factor-α

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology


Dive into the research topics of 'Loss of epidermal growth factor regulation by cobalamin in multiple sclerosis'. Together they form a unique fingerprint.

Cite this