IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis

Pinto, Vítor Laerte; Rebelo, Maria Cristina; Gomes, Rachel Novaes; Assis, Edson F. de; Castro‐Faria‐Neto, Hugo C.; Bóia, Márcio Neves

doi:10.1590/s1413-86702011000200011

Cited by 15 publications

(10 citation statements)

References 9 publications

(10 reference statements)

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“…10 However, conflicting results have been shown regarding the usefulness of IL-6 in CSF for diagnosing bacterial meningitis in children 25 and adults. 24,32 In addition to its diagnostic potential for early diagnosis of ventriculitis, IL-6 in CSF has also been investigated regarding its association with injury severity and neurological outcome. Initially, a neuroprotective effect by elevated IL-6 concentrations in CSF after TBI with improved clinical outcome was assumed.…”

Section: Discussionmentioning

confidence: 99%

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

Lenski

Biczok

Neufischer

et al. 2019

Neurosurgical Focus

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ObjectiveThe aim of this study was to investigate the diagnostic potential of the inflammatory markers interleukin-6 (IL-6), total leukocyte count (TLC), and protein in the CSF and IL-6, C-reactive protein, and white blood cell count in the serum for the early diagnosis of ventriculitis in patients with traumatic brain injury (TBI) and an external ventricular drain compared with patients without ventriculitis.MethodsRetrospective data from 40 consecutive patients with TBI and an external ventricular drain treated in the authors’ intensive care unit between 2013 and 2017 were analyzed. For all markers, arithmetical means and standard deviations, area under the curve (AUC), cutoff values, sensitivity, specificity, positive likelihood ratio (LR), and negative LR were calculated and correlated with presence or absence of ventriculitis.ResultsThere were 35 patients without ventriculitis and 5 patients with ventriculitis. The mean ± SD IL-6 concentration in CSF was significantly increased, with 6519 ± 4268 pg/mL at onset of ventriculitis compared with 1065 ± 1705 pg/mL in patients without ventriculitis (p = 0.04). Regarding inflammatory markers in CSF, IL-6 showed the highest diagnostic potential for differentiation between the presence and absence of ventriculitis (AUC 0.938, cutoff 4064 pg/mL, sensitivity 100%, specificity 92.3%, positive LR 13, and negative LR 0), followed by TLC (AUC 0.900, cutoff 64.5 /µL, sensitivity 100%, specificity 80%, positive LR 5.0, and negative LR 0) and protein (AUC 0.876, cutoff 31.5 mg/dL, sensitivity 100%, specificity 62.5%, positive LR 2.7, and negative LR 0).ConclusionsThe level of IL-6 in CSF has the highest diagnostic value of all investigated inflammatory markers for detecting ventriculitis in TBI patients at an early stage. In particular, CSF IL-6 levels higher than the threshold of 4064 pg/mL were significantly associated with the probability of ventriculitis.

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Section: Discussionmentioning

confidence: 99%

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

Lenski

Biczok

Neufischer

et al. 2019

Neurosurgical Focus

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“…These results indicate a predominately intrathecal production of these mediators in CNS infections. IL-6, IL-8, and TNF in CSF have in several studies been found to be elevated in meningitis and have even been proposed as biomarkers in CSF for bacterial meningitis [ 6 , 45 ]. We found a general increase for most of the inflammatory mediators in both ASM and ABM, and our study does not support the use of one particular cytokine as a diagnostic marker to distinguish ABM from other CNS conditions, including ASM.…”

Section: Discussionmentioning

confidence: 99%

High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infections

Quist‐Paulsen

Aukrust

Kran

et al. 2018

J Neuroinflammation

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BackgroundThe host response to intruders in the central nervous system (CNS) may be beneficial but could also be harmful and responsible for neurologic symptoms and sequelae in CNS infections. This immune response induces the activation of the kynurenine pathway (KP) with the production of neuroactive metabolites. Herein, we explored cytokine and KP responses in cerebrospinal fluid (CSF) and serum in patients with encephalitis, aseptic, and bacterial meningitis.MethodsCytokines were measured in CSF and serum by multiplex assay in adult patients with encephalitis of infectious, autoimmune or unknown etiology (n = 10), aseptic meningitis (ASM, n = 25), acute bacterial meningitis (ABM, n = 6), and disease control patients with similar symptoms but without pleocytosis in CSF (n = 42). Liquid chromatography-tandem mass spectrometry (LC-MS/ MS) was used to measure KP metabolites in CSF and serum.ResultsA characteristic pattern of increasing cytokine levels and KP metabolites was found in CSF from encephalitis to ASM, with the highest levels in ABM. In ASM and ABM, most inflammatory mediators, including IL-6, IL-8, and IFN-inducible protein-10 (IP-10), showed markedly elevated levels in CSF compared with serum, indicating production within the CNS. In contrast to most mediators, the highest level of IP-10 was found in the ASM group, suggesting a potential role for IP-10 in aseptic/viral meningitis. Neopterin and IP-10 were associated with marked changes in KP metabolites in CSF with increasing kynurenine/tryptophan ratio reflecting indoleamine 2,3-dioxygenase activity. Neopterin, a marker of IFN-γ activity, was associated with an unfavorable balance between neuroprotective and neurotoxic tryptophan metabolites.ConclusionWe show that parenchymal and meningeal inflammations in CNS share a characteristic cytokine profile with a general immune response in the CSF with limited influence from the systemic circulation. IFN-γ activity, assessed by neopterin and IP-10 levels, may play a role in the activation of the KP pathway in these patients, potentially mediating neurotoxic effects.Electronic supplementary materialThe online version of this article (10.1186/s12974-018-1366-3) contains supplementary material, which is available to authorized users.

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“…Previous works have investigated the CSF levels of inflammatory cytokines and chemokines in patients with meningitis, such as IL-6, IL-1β, TNF-α, IL-10, chemokines of the CXC family (IL-8) and growth factors using immunoenzymatic methods [ 23 - 30 ]. None of these proteins were detected in the present study using 2D PAGE followed by mass spectrometry.…”

Section: Discussionmentioning

confidence: 99%

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

et al. 2015

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BackgroundMeningitis is the inflammation of the meninges in response to infection or chemical agents. While aseptic meningitis, most frequently caused by enteroviruses, is usually benign with a self-limiting course, bacterial meningitis remains associated with high morbidity and mortality rates, despite advances in antimicrobial therapy and intensive care. Fast and accurate differential diagnosis is crucial for assertive choice of the appropriate therapeutic approach for each form of meningitis.MethodsWe used 2D-PAGE and mass spectrometry to identify the cerebrospinal fluid proteome specifically related to the host response to pneumococcal, meningococcal, and enteroviral meningitis. The disease-specific proteome signatures were inspected by pathway analysis.ResultsUnique cerebrospinal fluid proteome signatures were found to the three aetiological forms of meningitis investigated, and a qualitative predictive model with four protein markers was developed for the differential diagnosis of these diseases. Nevertheless, pathway analysis of the disease-specific proteomes unveiled that Kallikrein-kinin system may play a crucial role in the pathophysiological mechanisms leading to brain damage in bacterial meningitis. Proteins taking part in this cellular process are proposed as putative targets to novel adjunctive therapies.ConclusionsComparative proteomics of cerebrospinal fluid disclosed candidate biomarkers, which were combined in a qualitative and sequential predictive model with potential to improve the differential diagnosis of pneumococcal, meningococcal and enteroviral meningitis. Moreover, we present the first evidence of the possible implication of Kallikrein-kinin system in the pathophysiology of bacterial meningitis.

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IL-6 and IL-8 in cerebrospinal fluid from patients with aseptic meningitis and bacterial meningitis: their potential role as a marker for differential diagnosis

Cited by 15 publications

References 9 publications

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

Significance of cerebrospinal fluid inflammatory markers for diagnosing external ventricular drain–associated ventriculitis in patients with severe traumatic brain injury

High neopterin and IP-10 levels in cerebrospinal fluid are associated with neurotoxic tryptophan metabolites in acute central nervous system infections

Comparative proteomics of cerebrospinal fluid reveals a predictive model for differential diagnosis of pneumococcal, meningococcal, and enteroviral meningitis, and novel putative therapeutic targets

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