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 and might be influenced by dexamethasone.


RESULTS
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
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.
Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom.
Justin A
JA
Green
Chau T H
CT
Tran
Jeremy J
JJ
Farrar
Mai T H
MT
Nguyen
Phu H
PH
Nguyen
Sinh X
SX
Dinh
Nghia D T
ND
Ho
Chuong V
CV
Ly
Hien T
HT
Tran
Jon S
JS
Friedland
Guy E
GE
Thwaites
D000328:Adult; D002555:Cerebrospinal Fluid / Q000378:metabolism*; D017024:Chemotherapy, Adjuvant / Q000379:methods; D003907:Dexamethasone / Q000493:pharmacokinetics* / Q000627:therapeutic use; D005260:Female; D005938:Glucocorticoids / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D020782:Matrix Metalloproteinases / Q000378:metabolism*; D008875:Middle Aged; D009504:Neutrophils / Q000187:drug effects; D010919:Placebos; D016896:Treatment Outcome; D014390:Tuberculosis, Meningeal / Q000188:drug therapy*
D005938:Glucocorticoids; D010919:Placebos; D003907:Dexamethasone; D020782:Matrix Metalloproteinases; D020780:Matrix Metalloproteinase 9