Cerebrospinal Fluid Cytokines in Patients with Tuberculous Meningitis

Mastroianni, Claudio Maria; Paoletti, Francesca; Lichtner, Miriam; D’Agostino, Claudia; Vullo, Vincenzo; Delia, S.

doi:10.1006/clin.1997.4367

Cited by 78 publications

(60 citation statements)

References 27 publications

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“…As described previously in TBM (7,(15)(16)(17)(18), the cerebrospinal fluid contained a rich cytokine milieu; concentrations of IFN-␥, IL-6, IL-10, and IL-8 were high and remained elevated for several months. Of note, there was a trend toward decreased cerebrospinal fluid IFN-␥ concentrations in steroid-treated patients during the first week of therapy.…”

Section: Discussionmentioning

confidence: 52%

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

Simmons

Thwaites

Quyen

et al. 2005

The Journal of Immunology

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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-γ 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.

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Section: Discussionmentioning

confidence: 52%

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

Simmons

Thwaites

Quyen

et al. 2005

The Journal of Immunology

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“…The cytokine tumor necrosis factor alpha (TNF-␣) is critical in the neuropathogenesis of M. tuberculosis (42,124,221,224). Although TNF-␣ plays a definitive role in granuloma formation and containment of mycobacterial infections (58,99), local CNS production of TNF-␣ in experimental bacterial meningitis leads to altered blood-brain barrier (BBB) permeability and cerebrospinal fluid (CSF) leukocytosis (168,178,179) and has been implicated in fostering the progression of TBM in a murine model (224).…”

Section: Overview Of Pathogenesismentioning

confidence: 99%

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

et al. 2008

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SUMMARY Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.

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“…In contrast, HIV-1-coinfected individuals do show more frequent abnormalities such as space-occupying lesions or hydrocephalus on brain-imaging studies. Analysis of cytokines and chemokines in the CSF of patients with tuberculous meningitis shows elevated levels of IL-1␤, TNF-␣, IL-8, MCP-1, and macrophage inflammatory protein-1␣ (MIP-1␣), in amounts that are usually below those found in patients with bacterial meningitis but remain elevated for a much longer period after treatment (4,245,246,417). Acid-fast bacteria have been recovered from the CSF in as many as 91% of centrifuged specimens (370), but recovery is usually much lower than that due to low concentrations of bacteria in the CSF.…”

Section: Mycobacterium Tuberculosismentioning

confidence: 99%

Invasion of the Central Nervous System by Intracellular Bacteria

2004

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Infection of the central nervous system (CNS) is a severe and frequently fatal event during the course of many diseases caused by microbes with predominantly intracellular life cycles. Examples of these include the facultative intracellular bacteria Listeria monocytogenes, Mycobacterium tuberculosis, and Brucella and Salmonella spp. and obligate intracellular microbes of the Rickettsiaceae family and Tropheryma whipplei. Unfortunately, the mechanisms used by intracellular bacterial pathogens to enter the CNS are less well known than those used by bacterial pathogens with an extracellular life cycle. The goal of this review is to elaborate on the means by which intracellular bacterial pathogens establish infection within the CNS. This review encompasses the clinical and pathological findings that pertain to the CNS infection in humans and includes experimental data from animal models that illuminate how these microbes enter the CNS. Recent experimental data showing that L. monocytogenes can invade the CNS by more than one mechanism make it a useful model for discussing the various routes for neuroinvasion used by intracellular bacterial pathogens

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Cerebrospinal Fluid Cytokines in Patients with Tuberculous Meningitis

Cited by 78 publications

References 27 publications

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

The Clinical Benefit of Adjunctive Dexamethasone in Tuberculous Meningitis Is Not Associated with Measurable Attenuation of Peripheral or Local Immune Responses

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

Invasion of the Central Nervous System by Intracellular Bacteria

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