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  • Title: Matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of matrix metalloproteinase (TIMP-1) in patients with relapsing-remitting multiple sclerosis treated with interferon beta.
    Author: Boz C, Ozmenoglu M, Velioglu S, Kilinc K, Orem A, Alioglu Z, Altunayoglu V.
    Journal: Clin Neurol Neurosurg; 2006 Feb; 108(2):124-8. PubMed ID: 16412833.
    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 (IFNbeta) 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 IFNbeta-1a. PATIENTS AND METHODS: Blood and CSF samples from 14 patients with RRMS before and 6 months after IFNbeta 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 IFNbeta 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 IFNbeta therapy. CONCLUSIONS: Our result shows that RRMS patients have an impaired MMP-9 and TIMP-1 balance, and that 6 months of IFNbeta therapy is beneficial in restoring this balance.
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