Abstract
The pathogenesis of tuberculous meningitis remains unclear, and there are few data describing the kinetics of the immune response during the course of its treatment. We measured concentrations of pro- and anti-inflammatory cytokines in serial blood and cerebrospinal fluid (CSF) samples from 21 adults who were being treated for tuberculous meningitis. CSF concentrations of soluble tumor necrosis factor-alpha receptors and of matrix metalloprotein-9 and its tissue inhibitor were also measured, and blood-brain barrier permeability was assessed by the albumin and IgG partition indices. CSF concentrations of lactate, interleukin-8, and interferon-gamma were high before treatment and then decreased rapidly with antituberculosis chemotherapy. However, significant immune activation and blood-brain barrier dysfunction were still apparent after 60 days of treatment. Death was associated with high initial CSF concentrations of lactate, low numbers of white blood cells, in particular neutrophils, and low CSF glucose levels.
Highlights
Studies in rabbits have suggested that a central role exists for tumor necrosis factor (TNF)–a in the pathogenesis and progression of TBM [3]
A diagnosis of TBM was confirmed in 15 (71%) of 21
The cerebrospinal fluid (CSF) specimen taken at the end of antituberculosis chemotherapy (ATC) (9 months) served as an important indicator of successful treatment and as a control for those samples taken earlier in the infection
Summary
Studies in rabbits have suggested that a central role exists for tumor necrosis factor (TNF)–a in the pathogenesis and progression of TBM [3]. The mechanisms are probably multifactorial, the matrix metalloproteinases (MMPs) have been recently implicated [11] These molecules, which are secreted by monocytes and macrophages, are zinc-containing proteases that degrade extracellular matrix [12]. There are few studies that have described the expression of these molecules over the duration of treatment for TBM and their relationship with BBB dysfunction, clinical progression, and outcome after 9 months of antituberculosis chemotherapy (ATC). The purpose of the present study was to describe the effect of treatment on the constituents of the CSF—in particular the CSF expression of a range of pro- and anti-inflammatory molecules, MMP-9 and TIMP-1, and the integrity of the BBB— and to define which of the molecules carried prognostic significance. The HTD Scientific and Ethical Committee approved the study, and informed consent was obtained from all participants
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