MATRIX METALLOPROTEINASES AND TISSUE INHIBITORS OF METALLOPROTEINASESIN VIRAL MENINGITIS - UP-REGULATION OF MMP-9 AND TIMP-1 IN CEREBROSPINAL-FLUID

A hallmark of viral meningitis is the invasion of monocytes, lymphocyt es and, in the initial phase of the disease, neutrophils into the suba rachnoidal space. By their degradation of different macromolecular com ponents in the extracellular connective tissue, matrix metalloproteina ses (MMPs) may be essential for the breakdown of the vessel wall in th e meninges and the choroid plexus. In this study, the occurrence of MM P-1, MMP-2, MMP-3 and MMP-9 and the two tissue inhibitors of metallopr oteinases, TIMP-1 and TIMP-2, was monitored in the cerebrospinal fluid (CSF) from patients with viral meningitis. Of the proteinases, MMP-9 was found in 13 of 39 (33%) patients, but not in controls; the levels being correlated with the neutrophil cell number in CSF. The CSF conce ntration of TIMP-1 was increased three-fold compared to the control gr oup (median 233 ng/ml; range 9.4-1252.5 ng/ml) and was correlated to t he levels of total protein in CSF. Of the other MMPs and TIMPs assayed , MMP-2 and TIMP-2 were constitutively expressed and not upregulated i n viral meningitis. High levels of MMP-9 and MMP-2, as measured by ELI SA, was associated with high proteolytic activity detected in CSF by z ymography. In conclusion, invasion of the leukocytes into the CSF comp artment in viral meningitis may involve MMP-9, its proteolytic effect likely being controlled by expression of TIMP-1. (C) 1998 Elsevier Sci ence B.V.