PMID- 19789647
OWN - NLM
STAT- MEDLINE
DCOM- 20100201
LR  - 20220129
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 4
IP  - 9
DP  - 2009 Sep 30
TI  - Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and 
      clinical outcomes in tuberculous meningitis.
PG  - e7277
LID - 10.1371/journal.pone.0007277 [doi]
LID - e7277
AB  - 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.
FAU - Green, Justin A
AU  - Green JA
AD  - Department of Infectious Diseases and Immunity, Imperial College London, London, 
      United Kingdom.
FAU - Tran, Chau T H
AU  - Tran CT
FAU - Farrar, Jeremy J
AU  - Farrar JJ
FAU - Nguyen, Mai T H
AU  - Nguyen MT
FAU - Nguyen, Phu H
AU  - Nguyen PH
FAU - Dinh, Sinh X
AU  - Dinh SX
FAU - Ho, Nghia D T
AU  - Ho ND
FAU - Ly, Chuong V
AU  - Ly CV
FAU - Tran, Hien T
AU  - Tran HT
FAU - Friedland, Jon S
AU  - Friedland JS
FAU - Thwaites, Guy E
AU  - Thwaites GE
LA  - eng
GR  - WT_/Wellcome Trust/United Kingdom
GR  - G0500385/MRC_/Medical Research Council/United Kingdom
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, Non-U.S. Gov't
DEP - 20090930
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Glucocorticoids)
RN  - 0 (Placebos)
RN  - 7S5I7G3JQL (Dexamethasone)
RN  - EC 3.4.24.- (Matrix Metalloproteinases)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Adult
MH  - Cerebrospinal Fluid/*metabolism
MH  - Chemotherapy, Adjuvant/methods
MH  - Dexamethasone/*pharmacokinetics/therapeutic use
MH  - Female
MH  - Glucocorticoids/pharmacology
MH  - Humans
MH  - Kinetics
MH  - Male
MH  - Matrix Metalloproteinase 9/*metabolism
MH  - Matrix Metalloproteinases/*metabolism
MH  - Middle Aged
MH  - Neutrophils/drug effects
MH  - Placebos
MH  - Treatment Outcome
MH  - Tuberculosis, Meningeal/*drug therapy
PMC - PMC2748711
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2009/10/01 06:00
MHDA- 2010/02/02 06:00
PMCR- 2009/09/30
CRDT- 2009/10/01 06:00
PHST- 2009/07/21 00:00 [received]
PHST- 2009/08/26 00:00 [accepted]
PHST- 2009/10/01 06:00 [entrez]
PHST- 2009/10/01 06:00 [pubmed]
PHST- 2010/02/02 06:00 [medline]
PHST- 2009/09/30 00:00 [pmc-release]
AID - 09-PONE-RA-11755R1 [pii]
AID - 10.1371/journal.pone.0007277 [doi]
PST - epublish
SO  - PLoS One. 2009 Sep 30;4(9):e7277. doi: 10.1371/journal.pone.0007277.