Serum MMP-9/TIMP-1 and MMP-2/TIMP-2 ratios in multiple sclerosis: relationships with different magnetic resonance imaging measures of disease activity during IFN-beta-1a treatment

• Published in: Multiple sclerosis Vol. 11; no. 4; pp. 441 - 446
• Main Authors: Avolio, C, Filippi, M, Tortorella, C, Rocca, M A, Ruggieri, M, Agosta, F, Tomassini, V, Pozzilli, C, Stecchi, S, Giaquinto, P, Livrea, P, Trojano, M
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA SAGE Publications 01-08-2005; Arnold; Sage Publications Ltd
• Subjects: Adjuvants, Immunologic - therapeutic use; Biological and medical sciences; Blood-Brain Barrier; Brain - pathology; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Disease Progression; Drug Administration Schedule; Humans; Immunomodulators; Interferon beta-1a; Interferon-beta - therapeutic use; Magnetic Resonance Imaging; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 9 - blood; Medical sciences; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Multiple Sclerosis - pathology; Multiple sclerosis and variants. Guillain barré syndrome and other inflammatory polyneuropathies. Leukoencephalitis; Neurology; Pharmacology. Drug treatments; Recurrence; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Inhibitor of Metalloproteinase-2 - blood; interferon beta; MMP-9/TIMP-1; gadolinium triple dose; MMP-2/TIMP-2; MRI; multiple sclerosis; Multiple sclerosis; Central nervous system; MMP-9/T7MP-I; Metalloendopeptidases; Gadolinium; Blood brain barrier; Encephalon; Inflammatory disease; Degenerative disease; Interstitial collagenase; Human; Nervous system diseases; Enzyme; Chronic disease; Nuclear magnetic resonance imaging; Gelatinase B; Gelatinase A; Peptidases; Treatment; MW-2/T/MP-2; Central nervous system disease; Beta interferon; Hydrolases
• ISSN: 1352-4585; 1477-0970
• DOI: 10.1191/1352458505ms1193oa

Matrix metalloproteinase-9 (MMP-9) is involved in blood-brain barrier (BBB) disruption in active multiple sclerosis (MS), while MMP-2 seems to be associated with the chronic progressive phase of the disease. Recombinant interferon beta-1a (rIFNβ-1a) is effective in restoring the BBB. We studied the relationships between serum MMP-9, MMP-2, TIMP-1 and TIMP-2 and different magnetic resonance imaging (MRI) measures of disease activity in MS patients during treatment with rIFNβ-1a. Twenty-one relapsing-remitting (RR) MS patients underwent longitudinally simultaneous blood withdrawals and MRI (before and after standard dose (SD) and triple dose (TD) of gadolinium (Gd)) examinations before and during 48 weeks of rIFNβ-1a (Rebif® 22 mcg three times a week) treatment. Serum MMP-9, MMP-2, TIMP-1 and TIMP-2 were measured, MMP-9 to TIMP-1 and MMP-2 to TIMP-2 ratios were calculated and the numbers of Gd-SD, Gd-TD, new-Gd-SD, new-Gd-TD and new-T2 lesions counted. Serum MMP-9/TIMP-1 ratio (P< 0.0001), as well as the numbers of ‘active’ lesions (P ranging from 0.0004 to 0.005) decreased during treatment. Moreover, serum MMP-9/TIMP-1 ratio proved to be a good positive predictor (estimate= 0.85; P> 0.05) of the numbers of MRI Gd-TD active lesions. These data confirm that serum MMP-9/TIMP-1 ratio may be viewed as a reliable marker and may be predictive of MRI activity in RR MS.