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Cerebrospinal fluid cytokines in patients with tuberculous meningitis
C M Mastroianni1, F Paoletti, M Lichtner
1Department of Infectious and Tropical Diseases, La Sapienza University, Rome, Italy.
Insights
Tuberculous meningitis (TBM) is linked to increased levels of inflammatory cytokines like tumor necrosis factor-alpha and interferon-gamma in cerebrospinal fluid. These inflammatory markers persist long-term, indicating ongoing inflammation despite treatment.
Area of Science:
- Neuroscience
- Immunology
- Infectious Diseases
Background:
- Tuberculous meningitis (TBM) is a severe form of extrapulmonary tuberculosis affecting the central nervous system.
- Understanding the inflammatory milieu in the cerebrospinal fluid (CSF) is crucial for TBM pathogenesis and treatment monitoring.
Purpose of the Study:
- To investigate the levels and dynamics of key inflammatory cytokines and their receptors in the CSF of TBM patients.
- To explore the relationship between cytokine profiles, adenosine deaminase activity, and disease progression or outcome in TBM.
Main Methods:
- Measurement of tumor necrosis factor-alpha (TNF-alpha), soluble TNF receptors (sTNFR-75, sTNFR-55), interferon-gamma (IFN-gamma), interleukin-10 (IL-10), and IL-12 in 59 CSF samples from 15 TBM patients.
- Assessment of CSF adenosine deaminase (ADA) activity.
- Longitudinal monitoring of cytokine levels over time post-antibiotic therapy initiation.
Main Results:
- Elevated concentrations of TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10 were observed in TBM patients' CSF.
- CSF IL-12 was undetectable in all TBM patients.
- A significant correlation was found between cytokine levels and CSF ADA activity.
- TNF-alpha remained detectable for up to 16 months, while IFN-gamma, sTNFR-75, sTNFR-55, and IL-10 persisted for 4-8 months post-treatment.
- Chronic cytokine release was not associated with TBM stage or clinical outcome.
Conclusions:
- TBM is characterized by a sustained inflammatory response within the CSF compartment.
- The persistent elevation of cytokines suggests continuous inflammatory activity at the site of infection, independent of disease stage or clinical outcome.
- Cytokine profiles and ADA activity may serve as potential biomarkers in TBM, although their direct correlation with prognosis requires further investigation.
Abstract:
The level of tumor necrosis factor (TNF)-alpha, soluble TNF receptors p75 (sTNFR-75) and sTNFR-55, interferon (IFN)-gamma, and interleukin (IL)-10 and IL-12 were measured in 59 cerebrospinal fluid (CSF) samples from 15 patients with tuberculous meningitis (TBM). TBM was associated with elevated concentrations of TNF-alpha, sTNFR-75, sTNFR-55, IFN-gamma, and IL-10, while CSF IL-12 was undetectable in all TBM patients. A significant correlation between cytokines and CSF adenosine deaminase activity was also found. The levels of TNF-alpha did not decrease over time, being still detectable in the CSF 16 months after starting antibiotic therapy, whereas IFN-gamma along with anti-inflammatory mediators sTNFR-75, sTNFR-55, and IL-10 remained elevated in the CSF for 4-8 months. The chronic release of cytokines in the CSF compartment was related neither to the TBM stage nor to the clinical outcome of the disease, thus suggesting the presence of a continuous activity of the inflammatory process at the site of infection.