Balancing between apoptosis and survival biomarkers in the patients with tuberculous meningitis

The balancing factor of apoptosis, survival, inflammatory and oxidative stress biomarkers may determine the clinico-radiological severity and death in the patients with tuberculous meningitis (TBM).

We report the relationship of death [caspase-3, malondialdehyde (MDA), tumor necrosis factor-α (TNFα), interleukin 6 (IL6)] and survival biomarkers [X-linked inhibitory apoptotic protein (XIAP), IL10, glutathione (GSH) and catalase] in TBM, and its role in determining disease severity and death.

The diagnosis of TBM was based on clinical, MRI and cerebrospinal fluid (CSF) findings. Their clinical and MRI findings were noted. The severity of TBM was categorized as stages I to III. Serum and CSF caspase-3 and XIAP were measured by ELISA, and TNFα, IL6 and IL10 gene expression in peripheral blood mononuclear cells using RT-PCR (reverse-transcriptase polymerase chain reaction). Plasma MDA, GSH and catalase were measured by spectrophotometer.

There were 40 patients with TBM whose mean age was 31.6 years and 50% were females. TBM patients had higher expression of death (caspase-3, TNFα, IL6, and MDA) and suppression of survival biomarkers (XIAP, catalase and GSH) compared to the healthy controls. Caspase-3 positively correlated with TNFα, IL6 and MDA, and negatively with XIAP, GSH and catalase. Patients with longer duration of illness and definite TBM had higher expression of caspase-3. Patients who died has higher expression of caspase-3 and suppression of XIAP compared to those who survived.

It can be concluded from this study that there is up-regulation of death signals and suppression of survival signals in TBM.