Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis.
Dexamethasone, cerebrospinal fluid matrix metalloproteinase concentrations and clinical outcomes in tuberculous meningitis.
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DOI：
10.1371/journal.pone.0007277
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发表时间：
2009-09-30
期刊：
影响因子：
3.7
通讯作者：
Thwaites GE
中科院分区：
文献类型：
--
作者：
Green JA;Tran CT;Farrar JJ;Nguyen MT;Nguyen PH;Dinh SX;Ho ND;Ly CV;Tran HT;Friedland JS;Thwaites GE
辅助地塞米松可降低结核性脑膜炎的死亡率，但其如何产生这种效果尚不清楚。基质金属蛋白酶（MMPs）在许多炎症性中枢神经系统疾病的免疫病理中起重要作用，因此我们假设其分泌在TBM中起重要作用，并可能受到地塞米松的影响。在一组未感染HIV的成人（n = 37）中，研究了脑脊液（CSF） MMP和MMPs组织抑制剂（TIMPs）浓度的动力学，这些TBM患者被招募到一项随机、安慰剂对照的辅助地塞米松试验中。分析遵循预先定义的计划。地塞米松显著降低早期随访样本（治疗中位5天（范围3-8天））CSF MMP-9浓度，但对其他MMPs/TIMPs无显著影响。此外，脑脊液MMP-9浓度与伴随的脑脊液中性粒细胞计数密切相关。地塞米松在治疗早期降低脑脊液MMP-9浓度，这可能是皮质类固醇改善TBM预后的一种机制。脑脊液MMP-9与中性粒细胞计数之间的强相关性表明，多形核白细胞可能在TBM的早期发病机制中发挥核心作用。
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. 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. 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.
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DOI：
10.1165/ajrcmb.17.4.2877
发表时间：
1997-10-01
影响因子：
6.4
作者：
Okada, S;Kita, H;Leiferman, KM
通讯作者：
Leiferman, KM
影响因子：
--
作者：
Schoeman, JF;Elshof, JWM;Donald, PR
通讯作者：
Donald, PR
影响因子：
10
作者：
Chang, JC;Wysocki, A;Rom, WN
通讯作者：
Rom, WN
影响因子：
4.4
作者：
Lee, KY;Kim, EH;Heo, JH
通讯作者：
Heo, JH
影响因子：
6.1
作者：
Sellner, J;Leib, SL
通讯作者：
Leib, SL