Elevated Levels of MMP‐9 and TIMP‐1 in the Cerebrospinal Fluid of Children with Echovirus Type 30 and Mumps Meningitis

Abstract

Matrix metalloproteinases are involved in leucocyte invasion into the central nervous system (CNS) during meningitis. The aim of the study was to determine whether there are differences in the expression patterns of matrix metalloproteinase-9 (MMP-9) and the tissue inhibitor of metalloproteinase-1 (TIMP-1) in the cerebrospinal fluid (CSF) of patients with meningitis caused by one of two known distinct viral agents. Concentrations were measured by using an enzyme-linked immunosorbent assay (ELISA) in 16 children with mumps meningitis, in 25 children with echovirus type 30 meningitis and in a control group of 23 children without any CNS infection. Increased levels of MMP-9 were found in children with mumps (median 0.48 ng/ml; P < 0.001) and enteroviral meningitis (median 2.76 ng/ml; P < 0.001) compared with that in controls (median: 0.01 ng/ml). Concentrations of TIMP-1 greatly exceeded concentrations of MMP-9 and were elevated in children with mumps (median: 56 ng/ml) and echovirus type 30 meningitis (median: 55 ng/ml) compared to controls (median: 17 ng/ml). No significant differences in MMP-9 or TIMP-1 levels were detected between the two meningitis groups. The MMP-9/TIMP-1 ratio was greater in children with echovirus type 30 than in those with mumps meningitis. There was no correlation between MMP-9 levels and total CSF cell count. MMP-9 correlated with CSF absolute neutrophil count in children with echovirus type 30 meningitis (r = 0.431; P < 0.05). The concentration of MMP-9 is higher in children with viral meningitis, possibly because of infiltrating polymorphonuclear cells present in the initial phase of the disease.