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Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis.

Green, JA; Tran, CTH; Farrar, JJ; Nguyen, MTH; Nguyen, PH; Dinh, SX; Ho, NDT; Ly, CV; Tran, HT; Friedland, JS; et al. Green, JA; Tran, CTH; Farrar, JJ; Nguyen, MTH; Nguyen, PH; Dinh, SX; Ho, NDT; Ly, CV; Tran, HT; Friedland, JS; Thwaites, GE (2009) Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis. PLoS One, 4 (9). e7277. ISSN 1932-6203 https://doi.org/10.1371/journal.pone.0007277
SGUL Authors: Friedland, Jonathan Samuel

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Abstract

BACKGROUND: Adjunctive dexamethasone reduces mortality from tuberculous meningitis, but how it produces this effect is not known. Matrix metalloproteinases (MMPs) are important in the immunopathology of many inflammatory CNS diseases thus we hypothesized that that their secretion is important in TBM and might be influenced by dexamethasone. METHODOLOGY/PRINCIPAL FINDINGS: The kinetics of cerebrospinal fluid (CSF) MMP and tissue inhibitors of MMPs (TIMPs) concentrations were studied in a subset of HIV uninfected adults (n = 37) with TBM recruited to a randomized, placebo-controlled trial of adjuvant dexamethasone. Analysis followed a pre-defined plan. Dexamethasone significantly reduced CSF MMP-9 concentrations in early follow up samples (median 5 days (range 3-8) of treatment), but had no significant influence on other MMPs/TIMPs. Additionally CSF MMP-9 concentration was strongly correlated to concomitant CSF neutrophil count. CONCLUSIONS/SIGNIFICANCE: Dexamethasone decreased CSF MMP-9 concentrations early in treatment and this may represent one mechanism by which corticosteroids improve outcome in TBM. The strong correlation between CSF MMP-9 and neutrophil count suggests that polymorphonuclear leukocytes may play a central role in the early pathogenesis of TBM.

Item Type: Article
Additional Information: © 2009 Green et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Keywords: Adult, Cerebrospinal Fluid, Chemotherapy, Adjuvant, Dexamethasone, Female, Glucocorticoids, Humans, Kinetics, Male, Matrix Metalloproteinase 9, Matrix Metalloproteinases, Middle Aged, Neutrophils, Placebos, Treatment Outcome, Tuberculosis, Meningeal, Neutrophils, Cerebrospinal Fluid, Humans, Tuberculosis, Meningeal, Dexamethasone, Matrix Metalloproteinases, Placebos, Glucocorticoids, Treatment Outcome, Chemotherapy, Adjuvant, Kinetics, Adult, Middle Aged, Female, Male, Matrix Metalloproteinase 9, Science & Technology, Multidisciplinary Sciences, Science & Technology - Other Topics, MD Multidisciplinary, General Science & Technology
Journal or Publication Title: PLoS One
ISSN: 1932-6203
Language: eng
Dates:
DateEvent
30 September 2009Published
26 August 2009Accepted
Publisher License: Creative Commons: Attribution 4.0
Projects:
Project IDFunderFunder ID
UNSPECIFIEDWellcome Trusthttp://dx.doi.org/10.13039/100004440
G0500385Medical Research Councilhttp://dx.doi.org/10.13039/501100000265
PubMed ID: 19789647
Web of Science ID: WOS:000270354100025
Go to PubMed abstract
URI: http://openaccess.sgul.ac.uk/id/eprint/110608
Publisher's version: https://doi.org/10.1371/journal.pone.0007277

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