dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis地塞米松,脑脊液基质金属蛋白酶浓度和结核性脑膜炎的临床结果.pdfVIP

Dexamethasone, Cerebrospinal Fluid Matrix Metalloproteinase Concentrations and Clinical Outcomes in Tuberculous Meningitis 1 2 2 2 2 2 Justin A. Green *, Chau T. H. Tran , Jeremy J. Farrar , Mai T. H. Nguyen , Phu H. Nguyen , Sinh X. Dinh , 2 2 2 1 3 Nghia D. T. Ho , Chuong V. Ly , Hien T. Tran , Jon S. Friedland *, Guy E. Thwaites 1 Department of Infectious Diseases and Immunity, Imperial College London, London, United Kingdom, 2 Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam, 3 Centre for Molecular Microbiology and Infection, Imperial College London, London, United Kingdom 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