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


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.
Boz
Cavit
C
Department of Neurology, Faculty of Medicine, Karadeniz Technical University, 61080 Trabzon, Turkey. cavitb@yahoo.com
Ozmenoglu
Mehmet
M
Velioglu
Sibel
S
Kilinc
Kagan
K
Orem
Asim
A
Alioglu
Zekeriya
Z
Altunayoglu
Vildan
V
D000276:Adjuvants, Immunologic / Q000008:administration & dosage / Q000627:therapeutic use*; D000328:Adult; D016022:Case-Control Studies; D004334:Drug Administration Schedule; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D000068556:Interferon beta-1a; D016899:Interferon-beta / Q000008:administration & dosage / Q000627:therapeutic use*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood*; D008875:Middle Aged; D020529:Multiple Sclerosis, Relapsing-Remitting / Q000188:drug therapy / Q000378:metabolism*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000097:blood* / Q000134:cerebrospinal fluid*
D000276:Adjuvants, Immunologic; D019715:Tissue Inhibitor of Metalloproteinase-1; D016899:Interferon-beta; D020780:Matrix Metalloproteinase 9; D000068556:Interferon beta-1a