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Intrathecal synthesis of matrix metalloproteinase-9 in patients with multiple sclerosis: implication for pathogenesis

Department of Biochemistry and Molecular Biology, University of Bari, Bari, Italy, m.g.liuzzi{at}biologia.uniba.it

M Trojano

Department of Neurology and Psychiatric Sciences, University of Bari, Bari, Italy

M Fanelli

Department of Hygiene, University of Bari, Bari, Italy

C Avolio

University of Foggia, Italy

A Fasano

Department of Biochemistry and Molecular Biology, University of Bari, Bari, Italy

P Livrea

Department of Neurology and Psychiatric Sciences, University of Bari, Bari, Italy

P Riccio

Department of Biology D.B.A.F., University of Basilicata, Potenza, Italy

Matrix metalloproteinase-9 (MMP-9) was detected by zymography and enzyme-linked immunosorbent assay (ELISA) in matched serum and cerebrospinal fluid (CSF) samples from patients with neurological diseases. Patients with relapsing-remitting multiple sclerosis (RR-MS) had serum and CSF MMP-9 levels comparable to those from patients with inflammatory neurological diseases (INDs), but higher than patients with non-inflammatory neurological diseases (NINDs) and healthy donors (HDs). MMP-9 increased in active RR-MS in comparison with inactive RR-MS implying that MMP-9 in MS is related with clinical disease activity. A correlation between the CSF/serum albumin (Q_Alb) and CSF/serum MMP-9 (QMMP-9) was observed in IND and NIND but not in RR-MS patients, indicating that CSF MMP-9 levels in NIND and IND patients could be influenced by serum MMP-9 and blood-brain barrier (BBB) permeability properties. MS patients had higher values of QMMP-9:Q_Alb (MMP-9 index) than IND and NIND patients suggesting that in MS the increase in CSF MMP-9 could be due to intrathecal synthesis of MMP-9. A significant inverse correlation was found between MMP-9 and its endogenous inhibitor TIMP-1 in RR-MS indicating that in MS patients both the increase in MMP-9 and the decrease in TIMP-1 serum levels could contribute to BBB disruption and T-lymphocyte entry into the CNS.

Key Words: blood-brain barrier • cerebrospinal fluid • intrathecal synthesis • matrix metalloproteinases • MMP-9 index • multiple sclerosis • serum • TIMP-1

Multiple Sclerosis, Vol. 8, No. 3, 222-228 (2002)
DOI: 10.1191/1352458502ms800oa


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