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

Justin A Green1, Chau T H Tran, Jeremy J Farrar

  • 1Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.

Plos One
|October 1, 2009
PubMed
Abstract

Insights

Dexamethasone treatment for tuberculous meningitis (TBM) significantly reduced cerebrospinal fluid (CSF) MMP-9 levels, a key inflammatory marker. This suggests a potential mechanism for how corticosteroids improve TBM patient outcomes.

Area of Science:

  • Neuroscience
  • Immunology
  • Infectious Diseases

Background:

  • Tuberculous meningitis (TBM) is a severe infection with high mortality.
  • Adjunctive dexamethasone improves TBM outcomes, but its mechanism of action is unclear.
  • Matrix metalloproteinases (MMPs) are implicated in central nervous system (CNS) inflammation.

Purpose of the Study:

  • To investigate the role of MMPs in TBM pathogenesis.
  • To determine if dexamethasone influences MMP secretion in TBM patients.

Main Methods:

  • Cerebrospinal fluid (CSF) concentrations of MMPs and tissue inhibitors of MMPs (TIMPs) were analyzed.
  • Data from HIV-uninfected adults with TBM in a randomized, placebo-controlled dexamethasone trial were used.
  • Analysis focused on early treatment time points (median 5 days).

Main Results:

  • Dexamethasone significantly reduced CSF MMP-9 levels early in treatment.
  • No significant effect of dexamethasone was observed on other MMPs or TIMPs.
  • CSF MMP-9 concentrations strongly correlated with CSF neutrophil counts.

Conclusions:

  • Reduced CSF MMP-9 by dexamethasone may be a key mechanism for improved TBM outcomes.
  • High MMP-9 and neutrophil counts suggest polymorphonuclear leukocytes are critical in early TBM pathogenesis.
  • This study provides insights into the immunopathology of TBM and the effects of corticosteroid therapy.

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