Serum MMP-2 and MMP-9 are elevated in different multiple sclerosis subtypes

• Published in: Journal of neuroimmunology Vol. 136; no. 1; pp. 46 - 53
• Main Authors: Avolio, Carlo, Ruggieri, Maddalena, Giuliani, Fabrizio, Liuzzi, Grazia Maria, Leante, Rosaria, Riccio, Paolo, Livrea, Paolo, Trojano, Maria
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01-03-2003
• Subjects: Adult; Central Nervous System - immunology; Central Nervous System - metabolism; Central Nervous System - pathology; Cerebrospinal Fluid - cytology; Cerebrospinal Fluid - immunology; Female; Humans; Immunoglobulin G - blood; Leukocyte Count; Male; Matrix Metalloproteinase 2 - blood; Matrix Metalloproteinase 2 - immunology; Matrix Metalloproteinase 9 - blood; Matrix Metalloproteinase 9 - immunology; Matrix metalloproteinases; Middle Aged; Multiple sclerosis; Multiple Sclerosis - blood; Multiple Sclerosis - immunology; Nerve Fibers, Myelinated - immunology; Nerve Fibers, Myelinated - metabolism; Nerve Fibers, Myelinated - pathology; Tissue Inhibitor of Metalloproteinase-1 - blood; Tissue Inhibitor of Metalloproteinase-1 - immunology; Tissue Inhibitor of Metalloproteinase-2 - blood; Tissue Inhibitor of Metalloproteinase-2 - immunology; Tissue inhibitors of metalloproteinases; Up-Regulation - immunology; Tissue inhibitors of metalloproteinases; Multiple sclerosis; Matrix metalloproteinases
• ISSN: 0165-5728; 1872-8421
• DOI: 10.1016/S0165-5728(03)00006-7

In multiple sclerosis (MS), matrix metalloproteinase (MMP) activity in tissues is the result of a balance between MMPs and their tissue inhibitors (TIMPs). MMP-9 predominates in acute MS lesions and is inhibited by TIMP-1, while MMP-2 may participate in the remodeling of the extracellular matrix (ECM) such as in chronic disease and is inhibited by TIMP-2. These differences may be reflected in serum and cerebrospinal fluid (CSF). We have tried to characterize MMP-2 and MMP-9 activities, in relation to their respective TIMPs, 2 and 1, as a factor of different types of the disease, as this information was not previously clearly stated. We found the MMP-2/TIMP-2 ratio in serum to show higher values in secondary progressive (SP,
p=0.02) and primary progressive (PP,
p=0.01) MS than short disease duration (SDD) relapsing–remitting (RR) MS, but not different from the healthy control (HC) group. Whereas the MMP-9/TIMP-1 ratio in serum showed higher (
p=0.04) values in SDD RR MS than PP but also in active patients, evaluated either clinically (
p=0.006) or from the magnetic resonance imaging (MRI,
p<0.05), compared to inactive disease. CSF MMP to TIMP ratios did not differ between MS subtypes, suggesting systemic rather CNS-restricted changes. These results show that an increase in MMP-2/TIMP-2 ratio marks chronic progression in MS, but it is as high as in HC, and also confirm that high MMP-9 activity characterizes short duration relapsing and active forms of the disease.