Journal
MOLECULAR NEUROBIOLOGY
Volume 59, Issue 8, Pages 4869-4878Publisher
SPRINGER
DOI: 10.1007/s12035-022-02901-8
Keywords
TNF alpha; Caspase-3; IL6; Cytokine; Tuberculoma; Tuberculous meningitis; RT-PCR
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Funding
- Sanjay Gandhi Postgraduate Institute of Medical Sciences [A-04-PGI/IMP/76/2018]
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This study investigates the expression of TNF alpha, IL6, and caspase-3 in patients with tuberculous meningitis (TBM) and compares these biomarkers between patients with and without tuberculoma. The findings suggest that TNF alpha and IL6 are upregulated in patients with tuberculoma but downregulated in patients without tuberculoma. The expression of TNF alpha is positively correlated with caspase-3, and higher expression of TNF alpha and caspase-3 is associated with patient mortality.
The development of tuberculoma is a process of inflammation, necrosis, and apoptosis. Therefore, the pro-inflammatory cytokines and apoptosis biomarkers are likely to play an important role. In this study, we report the expression of TNF alpha, IL6, and caspase-3 at the mRNA level in the patients with tuberculous meningitis (TBM) and compare these biomarkers in the patients with and without tuberculoma. A total of 134 patients with TBM and 35 matched healthy controls were included. The clinical, cerebrospinal fluid (CSF), and cranial magnetic resonance imaging (MRI) findings were noted. The mRNA expression of TNF alpha, IL6, and caspase-3 in peripheral blood mononuclear cells was evaluated by reverse transcriptase polymerase chain reaction. On cranial MRI, 89 (64.2%) patients had tuberculoma, and their level of consciousness, severity of meningitis, CSF findings, and blood counts were not significantly different from those without tuberculoma. Patients with tuberculoma had a higher expression of TNF alpha and IL6 compared to the controls, but had lower expression compared to the patients without tuberculoma. TNF alpha expression positively correlated with the expression of caspase-3, but not with IL6. Twenty-five (18.6%) patients died: 12 (13.5%) in tuberculoma and 13 (28.9%) in the non-tuberculoma group. Death was related to higher expression of TNF alpha and caspase-3. The lower expression of TNF alpha and IL6 in intracranial tuberculoma suggests that these patients are unlikely to be benefited with TNF alpha blockers.
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