Abstract

Matrix Metalloproteases (MMPs) and cytokines have been involved in the pathogenesis of multiple sclerosis (MS). However, no studies have still explored the possible associations between the two families of molecules. The present study aimed to evaluate the contribution of active MMP-9, active MMP-2, interleukin- (IL-) 17, IL-18, IL-23, and monocyte chemotactic proteins-3 to the pathogenesis of MS and the possible interconnections between MMPs and cytokines. The proteins were determined in the serum and cerebrospinal fluid (CSF) of 89 MS patients and 92 other neurological disorders (OND) controls. Serum active MMP-9 was increased in MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP-2 and ILs did not change. CSF MMP-9, but not MMP-2 or ILs, was selectively elevated in MS compared to OND (p < 0.01). Regarding the MMPs and cytokines intercorrelations, we found a significant association between CSF active MMP-2 and IL-18 (r = 0.3, p < 0.05), while MMP-9 did not show any associations with the cytokines examined. Collectively, our results suggest that active MMP-9, but not ILs, might be a surrogate marker for MS. In addition, interleukins and MMPs might synergistically cooperate in MS, indicating them as potential partners in the disease process.

Highlights

  • Multiple sclerosis (MS) is a disease of the central nervous system (CNS) of supposed autoimmune origin, characterized by inflammation, demyelination, and neurodegeneration [1]

  • Serum active Matrix Metalloproteases (MMPs)-9 was increased in multiple sclerosis (MS) patients and other neurological disorders (OND) controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.), whereas active MMP2 and ILs did not change

  • We found a higher concentration of active MMP-9 in the serum of both MS patients and OND controls compared to healthy subjects (p < 0.001 and p < 0.01, resp.)

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Summary

Introduction

Multiple sclerosis (MS) is a disease of the central nervous system (CNS) of supposed autoimmune origin, characterized by inflammation, demyelination, and neurodegeneration [1]. The pathological features of the disease are heterogeneous, a common event is thought to be the reactivation within the CNS of infiltrating myelin-specific T cells which, in turn, trigger the recruitment of innate immunity cells mediating demyelination and axonal loss [2]. The perivascular transmigration and accumulation of inflammatory cells within the CNS are mainly mediated by two events: the production of leukocyte-attracting chemokines and the blood-brain barrier Disease Markers. Healthy controls (n = 40) OND (n = 92) MS (n = 89) Age. 37.0 ± 7.5; 35.5 (30.3–44.0). 39.2 ± 10.9; 37.0 (30.5–48.0) Sex: female/male

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