Elevation of matrix metalloproteinase-9 level in cerebrospinal fluid of tick-borne encephalitis patients is associated with IgG extravassation and disease severity

PLoS One. 2013 Nov 1;8(11):e77427. doi: 10.1371/journal.pone.0077427. eCollection 2013.

Abstract

Background: Tick-borne encephalitis (TBE), caused by tick-borne encephalitis virus (TBEV), is an infectious disease involving the central nervous system (CNS). The pathogenesis of CNS injury has not been clearly demonstrated. Matrix metalloproteinase-9 (MMP-9) and some cytokines, such as interleukin 6 (IL-6), may play important roles in the disruption of the blood-brain barrier (BBB) and the pathogenesis of TBE.

Methods: 72 cerebrospinal fluid (CSF) samples were collected from TBE patients in north eastern China. IgG levels in CSF and serum were compared and MMP-9 and IL-6 levels were evaluated by ELISA. The correlation between the elevated MMP-9 levels and IgG extravasation, disease severity, and neuroinflammation was analyzed.

Results: Increased concentration of MMP-9 was detected in some of the CSF samples, and the elevation was found to be closely related to CSF TBEV IgG extravasation and enhancement of IL-6 expression. Moreover, elevated levels of MMP-9 were found to be correlated with IL-6 enhancement. Four of the 72 patients, the ones who died, presented with high CSF MMP-9 levels.

Conclusions: In TBE patients, elevated CSF MMP-9 levels were associated with brain inflammatory reaction, disruption of the blood-brain barrier, and disease severity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Encephalitis, Tick-Borne / immunology
  • Encephalitis, Tick-Borne / metabolism*
  • Encephalitis, Tick-Borne / mortality
  • Encephalitis, Tick-Borne / pathology
  • Humans
  • Immunoglobulin G / blood
  • Immunoglobulin G / cerebrospinal fluid*
  • Interleukin-6 / metabolism
  • Matrix Metalloproteinase 9 / cerebrospinal fluid*
  • Severity of Illness Index

Substances

  • IL6 protein, human
  • Immunoglobulin G
  • Interleukin-6
  • MMP9 protein, human
  • Matrix Metalloproteinase 9

Grants and funding

This study was supported by National Key Research Special Foundation of China (Grant no. 2011ZX10004-001; 2013ZX10004606 and 2013ZX10004803) and National Nature Science Fund Committee (No,81171663). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.