2015•Unpublished venueRequires access

Do cytokines correlate with disease activity in tuberculous meningitis

Pranay Sinha, Manish Modi, Sudesh K. Prabhakar, Paramjit Singh

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Abstract

Background: Tuberculous meningitis (TBM) remains to be one of the most fatal central nervous system infections. The exact pathogenesis of TBM at cellular level remains unclear. In this study, we assessed the cytokine levels in the serum and cerebrospinal fluid (CSF) of TBM patients and determined their correlation with the disease activity. Methods: The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme linked immunosorbant assay (ELISA) in both serum and CSF of 38 patients at baseline, and in 17 of these patients at 1 and 6 month of follow-up. Clinical examination and imaging was performed at baseline and on follow-ups. Results: There was a remarkable rise in the levels of serum and CSF TNF-α and IL-1β in TBM patients as compared to age and sex matched controls (p<0.05). A significant correlation was found between cytokine levels and stages of TBM (p< 0.05). TNF-α levels in both serum and CSF and IL-1β levels in serum were found to be significantly higher in those patients who died than those who survived and had better outcome. TNF-α was higher in patients who developed tuberculoma on follow-up than those who did not (p<0.05). The cytokine levels progressively declined over time but remained detectable till 6 months in most patients. Conclusions: The higher levels of TNF-α and IL-1β were associated with poor outcome in TBM. The higher cytokine levels in patients developing tuberculoma on antituberculous therapy and steroids suggests that these patients may benefit from immunomodulation agents like anti-TNF-α antibody.

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What this paper is about

Background: Tuberculous meningitis (TBM) remains to be one of the most fatal central nervous system infections. The exact pathogenesis of TBM at cellular level remains unclear. In this study, we assessed the cytokine levels in the serum and cerebrospinal fluid (CSF) of TBM patients and determined their correlation with the disease activity. Methods: The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme linked immunosorbant assay (ELISA) in both serum and CSF of 38 patients at baseline, and in 17 of these patients at 1 and 6 month of follow-up. Clinical examination and imaging was performed at baseline and on follow-ups. Results: There was a remarkable rise in the levels of serum and CSF TNF-α and IL-1β in TBM patients as compared to age and sex matched controls (p<0.05). A significant correlation was found between cytokine levels and stages of TBM (p< 0.05). TNF-α levels in both serum and CSF and IL-1β levels in serum were found to be significantly higher in those patients who died than those who survived and had better outcome. TNF-α was higher in patients who developed tuberculoma on follow-up than those who did not (p<0.05). The cytokine levels progressively declined over time but remained detectable till 6 months in most patients. Conclusions: The higher levels of TNF-α and IL-1β were associated with poor outcome in TBM. The higher cytokine levels in patients developing tuberculoma on antituberculous therapy and steroids suggests that these patients may benefit from immunomodulation agents like anti-TNF-α antibody.

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Available abstract

Background: Tuberculous meningitis (TBM) remains to be one of the most fatal central nervous system infections. The exact pathogenesis of TBM at cellular level remains unclear. In this study, we assessed the cytokine levels in the serum and cerebrospinal fluid (CSF) of TBM patients and determined their correlation with the disease activity. Methods: The levels of tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) were measured by enzyme linked immunosorbant assay (ELISA) in both serum and CSF of 38 patients at baseline, and in 17 of these patients at 1 and 6 month of follow-up. Clinical examination and imaging was performed at baseline and on follow-ups. Results: There was a remarkable rise in the levels of serum and CSF TNF-α and IL-1β in TBM patients as compared to age and sex matched controls (p<0.05). A significant correlation was found between cytokine levels and stages of TBM (p< 0.05). TNF-α levels in both serum and CSF and IL-1β levels in serum were found to be significantly higher in those patients who died than those who survived and had better outcome. TNF-α was higher in patients who developed tuberculoma on follow-up than those who did not (p<0.05). The cytokine levels progressively declined over time but remained detectable till 6 months in most patients. Conclusions: The higher levels of TNF-α and IL-1β were associated with poor outcome in TBM. The higher cytokine levels in patients developing tuberculoma on antituberculous therapy and steroids suggests that these patients may benefit from immunomodulation agents like anti-TNF-α antibody.

Key concepts: Medicine, Tuberculous meningitis, Tuberculoma, Cytokine, Cerebrospinal fluid, Pathogenesis, Tumor necrosis factor alpha, Immunology

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