All issues > Volume 46(6); 2003

Original Article

J Korean Pediatr Soc. 2003;46(6):548-553. Published online June 15, 2003.

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

Ju Hee JH Yang¹, Min Hyuk MH Park¹, Jung-Yeon JY Shim¹, Hye Lim HL Jung¹, Moon Soo MS Park¹, Dong Hyuck DH Keum¹

¹Department of Pediatrics, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

Correspondence Jung-Yeon JY Shim ,Email: jyssim@hotmail.com

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 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.

Keywords :Viral meningitis, MMP-9, TIMP-1, Blood-brain barrier