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Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis
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...
Autores principales: | , , , , , , , , , , |
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Formato: | Texto |
Lenguaje: | English |
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Public Library of Science
2009
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748711/ https://www.ncbi.nlm.nih.gov/pubmed/19789647 http://dx.doi.org/10.1371/journal.pone.0007277 |
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author | Green, Justin A. Tran, Chau T. H. Farrar, Jeremy J. Nguyen, Mai T. H. Nguyen, Phu H. Dinh, Sinh X. Ho, Nghia D. T. Ly, Chuong V. Tran, Hien T. Friedland, Jon S. Thwaites, Guy E. |
author_facet | Green, Justin A. Tran, Chau T. H. Farrar, Jeremy J. Nguyen, Mai T. H. Nguyen, Phu H. Dinh, Sinh X. Ho, Nghia D. T. Ly, Chuong V. Tran, Hien T. Friedland, Jon S. Thwaites, Guy E. |
author_sort | Green, Justin A. |
collection | PubMed |
description | 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. |
format | Text |
id | pubmed-2748711 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2009 |
publisher | Public Library of Science |
record_format | MEDLINE/PubMed |
spelling | pubmed-27487112009-09-30 Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis Green, Justin A. Tran, Chau T. H. Farrar, Jeremy J. Nguyen, Mai T. H. Nguyen, Phu H. Dinh, Sinh X. Ho, Nghia D. T. Ly, Chuong V. Tran, Hien T. Friedland, Jon S. Thwaites, Guy E. PLoS One Research Article 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. Public Library of Science 2009-09-30 /pmc/articles/PMC2748711/ /pubmed/19789647 http://dx.doi.org/10.1371/journal.pone.0007277 Text en Green et al. http://creativecommons.org/licenses/by/4.0/ 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 properly credited. |
spellingShingle | Research Article Green, Justin A. Tran, Chau T. H. Farrar, Jeremy J. Nguyen, Mai T. H. Nguyen, Phu H. Dinh, Sinh X. Ho, Nghia D. T. Ly, Chuong V. Tran, Hien T. Friedland, Jon S. Thwaites, Guy E. Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title | Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title_full | Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title_fullStr | Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title_full_unstemmed | Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title_short | Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis |
title_sort | dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2748711/ https://www.ncbi.nlm.nih.gov/pubmed/19789647 http://dx.doi.org/10.1371/journal.pone.0007277 |
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