Concentration gradient of CXCL10 and CXCL11 between the cerebrospinal fluid and plasma in children with enteroviral aseptic meningitis

Čavčić, Anamarija; Tešović, Goran; Gorenec, Lana; Grgić, Ivo; Benić, Branka; Lepej, Snježana Židovec

doi:10.1016/j.ejpn.2011.05.008

Cited by 16 publications

(8 citation statements)

References 28 publications

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“…On the other hand, the induction of a tolerogenic state could warrant the recurrent episodes of HSM. CXCL11 expression is not unique for HSM as it has been observed in neuroborreliosis and enteroviral meningitis [45, 46]. However, the levels of CXCL11 were modest compared to HSM.…”

Section: Discussionmentioning

confidence: 97%

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis

Lind¹,

Studahl²,

Berg³

et al. 2017

J Neuroinflammation

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BackgroundThe closely related herpes simplex viruses 1 and 2 can cause inflammations of the central nervous system (CNS), where type 1 most often manifest as encephalitis (HSE), and type 2 as meningitis (HSM). HSE is associated with severe neurological complications, while HSM is benign in adults. We proposed that studying the chemokine and cytokine production in cerebrospinal fluid (CSF) and serum could indicate why two closely related viruses exhibit different severity of their accompanied CNS inflammation.MethodsSecretion patterns of 30 chemokines and 10 cytokines in CSF of adult patients with acute HSE (n = 14) and HSM (n = 20) in the initial stage of disease were analyzed and compared to control subjects without viral central nervous system infections and to levels in serum.ResultsMost measured chemokines and cytokines increased in CSF of HSE and HSM patients. Overall, the CSF chemokine levels were higher in CSF of HSM patients compared to HSE patients. However, only five chemokines reached levels in the CSF that exceeded those in serum facilitating a positive CSF-serum chemokine gradient. Of these, CXCL8, CXCL9, and CXCL10 were present at high levels both in HSE and HSM whereas CXCL11 and CCL8 were present in HSM alone. Several chemokines were also elevated in serum of HSE patients but only one in HSM patients. No chemokine in- or efflux between CSF and serum was indicated as the levels of chemokines in CSF and serum did not correlate.ConclusionsWe show that HSM is associated with a stronger and more diverse inflammatory response in the CNS compared to HSE in the initial stage of disease. The chemokine patterns were distinguished by the exclusive local CNS production of CXCL11 and CCL8 in HSM. Inflammation in HSM appears to be restricted to the CNS whereas HSE also was associated with systemic inflammation.Electronic supplementary materialThe online version of this article (doi:10.1186/s12974-017-0907-5) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 97%

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis

Lind¹,

Studahl²,

Berg³

et al. 2017

J Neuroinflammation

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“…The chemokine CXCL10, also called interferon (IFN) γ-inducible protein 10 (IP-10), is produced by innate immune cells, such as neutrophils, and it stimulates chemotaxis of mononuclear cells into the CNS in response to meningitis/encephalitis caused by, for instance, enterovirus [43], B. burgdorferi [44], and TBE virus [45]. Furthermore, IP-10 has been proposed as a potential discriminator between bacterial and viral CNS infections [41].…”

Section: Discussionmentioning

confidence: 99%

“…CSF samples from 111 well-characterised children (64 girls, 47 boys; median age, 10 years; interquartile range [IQR], 5-15 years) with definitive or possible LNB (N = 28), tick-borne encephalitis (TBE; N = 3), enteroviral meningitis (EVM; N = 7), other viral infection (OVI, N = 4), and other non-infectious disorders with neurological or CNS symptoms without pleocytosis (N = 69; as described in Table 1) were obtained by lumbar puncture prospectively during the period 2010-2014 as part of a multi-centre study evaluating children with suspected LNB in Sweden, as previously reported [23]. LNB was Cells 2020, 9,43 3 of 14 diagnosed according to European guidelines [7]. Definite LNB (N = 20) was defined as the presence of: (i) symptoms attributable to LNB, (ii) mononuclear pleocytosis in the CSF, and (iii) intrathecally produced anti-Borrelia antibodies.…”

Section: Paediatric Patientsmentioning

confidence: 99%

“…D'Agostino and Pearson omnibus normality tests were used to determine whether or not the data for continuous variables had a Gaussian distribution. For a non-Gaussian distribution of the data, the Mann-Whitney U-test was applied in comparisons between two groups with independent Cells 2020, 9,43 6 of 14 observations. The Kruskal-Wallis test was used for comparisons of more than two groups and if the Kruskal-Wallis test result was significant, Dunn's post hoc test was performed.…”

Section: Statisticsmentioning

confidence: 99%

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Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

Söderberg

Enocsson

Skogman

et al. 2019

Cells

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Neutrophils operate as part of the innate defence in the skin and may eliminate the Borrelia spirochaete via phagocytosis, oxidative bursts, and hydrolytic enzymes. However, their importance in Lyme neuroborreliosis (LNB) is unclear. Neutrophil extracellular trap (NET) formation, which is associated with the production of reactive oxygen species, involves the extrusion of the neutrophil DNA to form traps that incapacitate bacteria and immobilise viruses. Meanwhile, NET formation has recently been studied in pneumococcal meningitis, the role of NETs in other central nervous system (CNS) infections has previously not been studied. Here, cerebrospinal fluid (CSF) samples from clinically well-characterised children (N = 111) and adults (N = 64) with LNB and other CNS infections were analysed for NETs (DNA/myeloperoxidase complexes) and elastase activity. NETs were detected more frequently in the children than the adults (p = 0.01). NET presence was associated with higher CSF levels of CXCL1 (p < 0.001), CXCL6 (p = 0.007), CXCL8 (p = 0.003), CXCL10 (p < 0.001), MMP-9 (p = 0.002), TNF (p = 0.02), IL-6 (p < 0.001), and IL-17A (p = 0.03). NETs were associated with fever (p = 0.002) and correlated with polynuclear pleocytosis (r s = 0.53, p < 0.0001). We show that neutrophil activation and active NET formation occur in the CSF samples of children and adults with CNS infections, mainly caused by Borrelia and neurotropic viruses. The role of NETs in the early phase of viral/bacterial CNS infections warrants further investigation. supervision, C.S., D.N. and L.E.M.; project administration, J.S.; funding, D.A., B.H.S., D.N., L.E.M. and C.S.; acquisition, D.A., L.E.M., C.S. and J.S. All authors have read and agreed to the published version of the manuscript.

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“…In addition, these increased levels of OTA correlated with elevated levels of activated CD4 T cells (CCR5+ and HLA-DR+) and an inflammatory chemokine associated with Th1 T cell mobilization and activation, CXCL10. Increased HLA-DR, CCR5, and CXCL10 expression has been implicated in the pathogenesis of key causes of infant mortality in Africa, including HIV ( 38 , 48 – 50 ), lower-respiratory infections ( 51 , 52 ), sepsis ( 53 ), encephalopathy ( 54 ), and meningitis ( 55 ). While we cannot rule out that plasma OTA levels are merely a biomarker for increased food antigen exposure, our study is the first to identify OTA at high levels in infants consuming non-breast milk foods.…”

Section: Discussionmentioning

confidence: 99%

T Cell Activation in South African HIV-Exposed Infants Correlates with Ochratoxin A Exposure

Wood

Fisher

et al. 2017

Front. Immunol.

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The introduction of non-breastmilk foods to HIV-infected infants is associated with increased levels of immune activation, which can impact the rate of HIV disease progression. This is particularly relevant in countries where mother-to-child transmission of HIV still occurs at unacceptable levels. The goal of this study was to evaluate the levels of the toxic food contaminant ochratoxin A (OTA) in HIV-exposed South African infants that are either breastfed or consuming non-breast milk foods. OTA is a common mycotoxin, found in grains and soil, which is toxic at high doses but has immunomodulatory properties at lower doses. Samples from HIV-exposed and HIV-unexposed infants enrolled in prospective observational cohort studies were collected and analyzed at birth through 14 weeks of age. We observed that infants consuming non-breast milk foods had significantly higher plasma levels of OTA at 6 weeks of age compared to breastfed infants, increasing until 8 weeks of age. The blood levels of OTA detected were comparable to levels observed in OTA-endemic communities. OTA plasma levels correlated with HIV target cell activation (CCR5 and HLADR expression on CD4+ T cells) and plasma levels of the inflammatory cytokine CXCL10. These findings provide evidence that elevated OTA levels in South African infants are associated with the consumption of non-breastmilk foods and activation of the immune system. Reducing infant OTA exposure has the potential to reduce immune activation and provide health benefits, particularly in those infants who are HIV-exposed or HIV-infected.

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Concentration gradient of CXCL10 and CXCL11 between the cerebrospinal fluid and plasma in children with enteroviral aseptic meningitis

Cited by 16 publications

References 28 publications

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis

CXCL11 production in cerebrospinal fluid distinguishes herpes simplex meningitis from herpes simplex encephalitis

Neutrophil Extracellular Traps (NETs) in the Cerebrospinal Fluid Samples from Children and Adults with Central Nervous System Infections

T Cell Activation in South African HIV-Exposed Infants Correlates with Ochratoxin A Exposure

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