Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple sclerosis treated with interferon beta


Boz C., Ozmenoglu M., Velioglu S., Kilinc K., Orem A., Alioglu Z., ...More

Clinical Neurology and Neurosurgery, vol.108, no.2, pp.124-128, 2006 (Peer-Reviewed Journal) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 108 Issue: 2
  • Publication Date: 2006
  • Doi Number: 10.1016/j.clineuro.2005.01.005
  • Journal Name: Clinical Neurology and Neurosurgery
  • Journal Indexes: Science Citation Index Expanded, Scopus
  • Page Numbers: pp.124-128
  • Keywords: MMP-9, TIMP-1, matrix metalloproteinase-9, multiple sclerosis, interferon beta, EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS, GELATINASE B, CEREBROSPINAL-FLUID, NERVOUS-SYSTEM, SERUM-LEVELS, IFN-BETA, PATHOGENESIS, CSF, MINOCYCLINE, EXPRESSION

Abstract

Objectives: Matrix metalloproteinases (MMPs), particularly MMP-9, facilitate T-cell migration into the central nervous system. They play a key role in the disruption of the blood-brain barrier (BBB) and thus in the pathogenesis of multiple sclerosis. Interferon beta's (IFNβ) ability to alter the balance between MMP-9 and MMP-9s natural inhibitor, tissue inhibitor of matrix metalloproteinase-1 (TIMP-1), may play a role in stabilizing the BBB. The aim of this study, was to evaluate serum MMP-9 and TIMP-1 and cerebrospinal fluid (CSF) TIMP-1 levels in patients with relapsing-remitting multiple sclerosis (RRMS) treated with IFNβ-1a. Patients and methods: Blood and CSF samples from 14 patients with RRMS before and 6 months after IFNβ therapy and 14 age and sex-matched controls were obtained. Levels of MMP-9 and TIMP-1 were measured using ELISA. Results: Before treatment, patients with MS had higher levels of serum MMP-9 and a higher MMP-9/TIMP-1 ratio than the controls. Although serum levels of TIMP-1 were lower in RRMS patients than in the controls, the differences did not reach statistical significance. CSF levels of TIMP-1 were significantly lower in RRMS patients. In the sixth month of IFNβ therapy serum MMP-9 and the MMP-9/TIMP-1 ratio were significantly decreased, whereas the changes in serum TIMP-1 were not statistically significant. There was a significant increase in CSF TIMP-1 levels in the sixth month of IFNβ therapy. Conclusions: Our result shows that RRMS patients have an impaired MMP-9 and TIMP-1 balance, and that 6 months of IFNβ therapy is beneficial in restoring this balance. © 2005 Elsevier B.V. All rights reserved.