Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India

Sharma, Sadhna; Goyal, Manoj; Sharma, Kusum; Modi, Manish; Sharma, Megha; Khandelwal, Niranjan; Prabhakar, Sudesh; Sharma, Navneet; Shree, Ritu; Gairolla, Jitender; Jain, Anshul; Lal, Vivek

doi:10.1016/j.jns.2017.06.001

Cited by 43 publications

(30 citation statements)

References 15 publications

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“…15 Also, there have been many attempts to investigate biomarkers to diagnose TBM. [16][17][18][19][20] Although immunity against M. tuberculosis is not fully understood, immunological markers associated with the host-M. tuberculosis interaction are considered as potential biomarkers for diagnosis. Previous studies have suggested that some cytokines and chemokines could be such biomarkers.…”

Section: Introductionmentioning

confidence: 99%

Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Kwon

Park

Kim

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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In this study, we investigated the diagnostic utility of the cytokine profile of the cerebrospinal fluid (CSF) and enzyme-linked immunospot (ELISPOT) assays of patients with suspected tuberculous meningitis (TBM). We prospectively enrolled adult patients with suspected TBM, and CSF specimens were analyzed for 18 cytokines/chemokines and soluble programmed death protein 1 (PD-1) and programmed death ligand 1 (PD-L1). Enzyme-linked immunospot assays were performed on mononuclear cells from the CSF (CSF-MCs) and peripheral blood (PBMCs). A total of 87 patients with meningitis, including 42 TBM-suspected patients and 45 non-TBM patients, were enrolled. Excluding the 32 patients with possible TBM, 10 patients with TBM and 45 patients with non-TBM were finally analyzed. Levels of adenosine deaminase (ADA), interleukin 12 subunit β (IL-12p40), IL-13, macrophage inflammatory protein α (MIP-1α), and soluble PD-1 and PD-L1 in the CSF were significantly higher in the TBM group than in the non-TBM group (P < 0.05). The optimal cutoff values for the sensitivities and specificities of the test methods for diagnosing TBM with small samples of 10 cases of definite or probable TBM were as follows:

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Section: Introductionmentioning

confidence: 99%

Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Kwon

Park

Kim

et al. 2019

The American Journal of Tropical Medicine and Hygiene

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“…In 118 adult TBM patients in India, aspirin resulted in absolute risk reduction of stroke in 19.1% and significant reduction in mortality compared to placebo (10 of 118 (21.7%) versus 23 of 118 (43.4%), p=0.02) 28 . A randomised controlled trial of TBM involving children in South Africa (n=146) could not establish improved neurological/cognitive outcomes or survival with aspirin at doses of 75 mg (low dose) or 100 mg/kg/day (high dose) 30 . However, the developmental outcome of children on high dose aspirin was similar to the placebo and low dose aspirin groups, despite being younger of age and having higher baseline severity.…”

Section: Promising Host Directed Therapies For Tuberculous Meningitismentioning

confidence: 97%

“…Non-steroidal inflammatory drugs (NSAIDs), which exert their effects by inhibiting cyclooxygenase (COX) activity may lead to reduction of excessive inflammation in TBM. As discussed, aspirin, a non-selective COX inhibitor, has been investigated in three trials in TBM with variable outcomes 27,28,30 . New generation NSAIDs with more selective inhibition of COX2 may have more favourable safety profiles.…”

Section: Eicosanoid Modulating Drugsmentioning

confidence: 99%

Host Directed Therapies for Tuberculous Meningitis

et al. 2021

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A dysregulated host immune response significantly contributes to morbidity and mortality in tuberculous meningitis (TBM). Effective host directed therapies (HDTs) are critical to improve survival and clinical outcomes. Currently only one HDT, dexamethasone, is proven to improve mortality. However, there is no evidence dexamethasone reduces morbidity, how it reduces mortality is uncertain, and it has no proven benefit in HIV co-infected individuals. Further research on these aspects of its use, as well as alternative HDTs such as aspirin, thalidomide and other immunomodulatory drugs is needed. Based on new knowledge from pathogenesis studies, repurposed therapeutics which act upon small molecule drug targets may also have a role in TBM. Here we review existing literature investigating HDTs in TBM, and propose new rationale for the use of novel and repurposed drugs. We also discuss host variable responses and evidence to support a personalised approach to HDTs in TBM.

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“…Furthermore, certain serum and CSF cytokines have been shown to be associated with disease outcomes in TBM [14,15]. High serum and CSF levels of IL-4 and IL-1β correlates with presence of infarcts on MRI brain [15]. In a recent study, elevated lumbar and ventricular CSF TNF-α, macrophage inflammatory protein 1α, IL-6, IL-8, as well as markers of brain injury were associated with infarcts in patients with TBM [8].…”

Section: Introductionmentioning

confidence: 96%

“…Upregulation of inflammatory mediators including tumour necrosis factor (TNF)-α, interferon (IFN)-γ, interleukin (IL)-1β, IL-6, IL-8 and IL-10 in the cerebrospinal fluid (CSF) of patients with TBM have been described [10][11][12][13], when compared to symptomatic controls. Furthermore, certain serum and CSF cytokines have been shown to be associated with disease outcomes in TBM [14,15]. High serum and CSF levels of IL-4 and IL-1β correlates with presence of infarcts on MRI brain [15].…”

Section: Introductionmentioning

confidence: 99%

Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis

et al. 2021

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Introduction Stroke is a common complication in children with tuberculous meningitis (TBM). Host proteins may give us insight into the mechanisms of stroke in TBM and serve as biomarkers for detection of stroke, however, they have not been widely explored. In this study, we compared the concentrations of cerebrospinal fluid (CSF) and serum proteins between children who had TBM-related stroke and children with TBM without stroke. Methods We collected CSF and serum from 47 children consecutively admitted to the Tygerberg Academic Hospital in Cape Town, South Africa between November 2016, and November 2017, on suspicion of having TBM. A multiplex platform was used to measure the concentrations of 69 host proteins in CSF and serum from all study participants. Results After classification of study participants, 23 (48.9%) out of the 47 study participants were diagnosed with TBM, of which 14 (60.9%) demonstrated radiological arterial ischemic infarction. The levels of lipocalin-2, sRAGE, IP-10/ CXCL10, sVCAM-1, MMP-1, and PDGF-AA in CSF samples and the levels of D-dimer, ADAMTS13, SAA, ferritin, MCP-1/ CCL2, GDF-15 and IL-13 in serum samples were statistically different between children who had TBM-related stroke and children with TBM without stroke. After correcting for multiple testing, only the levels of sVCAM-1, MMP-1, sRAGE, and IP-10/ CXCL10 in CSF were statistically different between the two groups. CSF and serum protein biosignatures indicated stroke in children diagnosed with TBM with up to 100% sensitivity and 88.9% specificity. Conclusion Serum and CSF proteins may serve as biomarkers for identifying individuals with stroke amongst children diagnosed with TBM at admission and may guide us to understand the biology of stroke in TBM. This was a pilot study, and thus further investigations in larger studies are needed.

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Cytokines do play a role in pathogenesis of tuberculous meningitis: A prospective study from a tertiary care center in India

Cited by 43 publications

References 15 publications

Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Diagnostic Usefulness of Cytokine and Chemokine Levels in the Cerebrospinal Fluid of Patients with Suspected Tuberculous Meningitis

Host Directed Therapies for Tuberculous Meningitis

Serum and cerebrospinal fluid host proteins indicate stroke in children with tuberculous meningitis

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