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Outcome from tuberculous meningitis (TBM) is believed to be dependent on the severity of the intracerebral inflammatory response. We have recently shown that dexamethasone improved survival in adults with TBM and postulated that the clinical effect would be associated with a measurable systemic and intracerebral impact on immunological markers of inflammation. Prolonged inflammatory responses were detected in all TBM patients irrespective of treatment assignment (placebo or dexamethasone). The inflammatory response in the cerebrospinal fluid was characterized by a leukocytosis (predominantly CD3(+)CD4(+) T lymphocytes, phenotypically distinct from those in the peripheral blood), elevated concentrations of inflammatory and anti-inflammatory cytokines, chemokines, and evidence of prolonged blood-brain barrier dysfunction. Dexamethasone significantly modulated acute cerebrospinal fluid protein concentrations and marginally reduced IFN-gamma concentrations; other immunological and routine biochemical indices of inflammation were unaffected. Peripheral blood monocyte and T cell responses to Mycobacterium tuberculosis Ags were also unaffected. Dexamethasone does not appear to improve survival from TBM by attenuating immunological mediators of inflammation in the subarachnoid space or by suppressing peripheral T cell responses to mycobacterial Ags. These findings challenge previously held theories of corticosteroid action in this disease. An understanding of how dexamethasone acts in TBM may suggest novel and more effective treatment strategies.

Original publication

DOI

10.4049/jimmunol.175.1.579

Type

Journal article

Journal

J Immunol

Publication Date

01/07/2005

Volume

175

Pages

579 - 590

Keywords

Adolescent, Adult, Aged, Anti-Inflammatory Agents, Antigens, Bacterial, Chemokines, Chemotherapy, Adjuvant, Cytokines, Dexamethasone, Double-Blind Method, Female, Humans, In Vitro Techniques, Interferon-gamma, Lymphocyte Subsets, Male, Middle Aged, Mycobacterium tuberculosis, Tuberculosis, Meningeal