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

Yang, Ju Hee; Park, Min Hyuk; Shim, Jung Yeon; Jung, Hye Lim; Park, Moon Soo; Keum, Dong Hyuck

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.