Pathophysiology and prognosis in vietnamese adults with tuberculous meningitis.
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.
Thwaites
Guy E
GE
Oxford University Clinical Research Unit, Ho Chi Minh City, Vietnam. gthwaites@hcm.vnn.vn.
Simmons
Cameron P
CP
Than Ha Quyen
Nguyen
N
Thi Hong Chau
Tran
T
Phuong Mai
Pham
P
Thi Dung
Nguyen
N
Hoan Phu
Nguyen
N
White
Nicholas P
NP
Tinh Hien
Tran
T
Farrar
Jeremy J
JJ
D000328:Adult; D000995:Antitubercular Agents / Q000627:therapeutic use; D001812:Blood-Brain Barrier / Q000502:physiology*; D016207:Cytokines / Q000097:blood* / Q000134:cerebrospinal fluid*; D006801:Humans; D007371:Interferon-gamma / Q000134:cerebrospinal fluid; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D007773:Lactates / Q000134:cerebrospinal fluid; D020780:Matrix Metalloproteinase 9 / Q000134:cerebrospinal fluid; D011379:Prognosis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000134:cerebrospinal fluid; D014390:Tuberculosis, Meningeal / Q000188:drug therapy / Q000382:microbiology / Q000503:physiopathology*; D014409:Tumor Necrosis Factor-alpha / Q000134:cerebrospinal fluid; D014744:Vietnam
D000995:Antitubercular Agents; D016207:Cytokines; D016209:Interleukin-8; D007773:Lactates; D019715:Tissue Inhibitor of Metalloproteinase-1; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma; D020780:Matrix Metalloproteinase 9