Increased Matrix Metalloproteinase-9 and Tissue Inhibitor of Metalloproteinase-1 Levels in the Cerebrospinal Fluid from Children with Aseptic Meningitis

ABSTRACT

PURPOSE: Matrix metalloproteinase(MMP)-9 is known to breakdown the blood-brain barrier by degrading the extracellular matrix of the subendothelial basement membrane in meningitis. Tissue inhibitor of metalloproteinase(TIMP)-1, a known inhibitor of MMP-9, has been postulated to inhibit the proteolytic activity of MMP-9 by bindng to MMP-9, but their interaction has not been fully understood yet. So far, there have been some reports on the relationship of MMP-9 and TIMP-1 in bacterial meningitis, but few reports in viral meningitis. Furthermore, there has been no report on this in Korea. We investigated the concentrations of MMP-9 and TIMP-1 in cerebrospinal fluid (CSF) and serum of patients with viral meningitis and control subjects, and evaluated their relationship with other clinical parameters of meningitis. METHODS: CSF and blood were obtained from 25 subjects with viral meningitis and 14 control subjects. After centrifugation, supernatants were stored at -20 degrees C and we assayed concentrations of MMP-9 and TIMP-1 by the sandwich ELISA method. RESULTS: Concentrations of CSF MMP-9 and TIMP-1 were significantly elevated in patients with viral meningitis, when compared with those in control subjects. Their serum levels showed no differences between the two groups. MMP-9 levels were closely correlated with TIMP-1 levels in the CSF(rs=0.42, P<0.05). CSF MMP-9/TIMP-1 ratios were significantly higher in patients with viral meningitis than those in the control subjects(P<0.05). Both CSF MMP-9 and TIMP-1 levels positively correlated with CSF total leukocyte counts(rs=0.43, P<0.05, rs=0.48, P<0.05). TIMP-1 levels positively correlated with total protein concentrations in the CSF(rs=0.43, P<0.05). CONCLUSION: MMP-9 and TIMP-1 may play an important role in the breakdown and maintenance of BBB in viral meningitis, respectively.