Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis

Kornelisse, René F.; Hack, C. E.; Savelkoul, H.F.J.; Kraan, Tineke C. T. M. van der Pouw; Hop, Wim C. J.; Mierlo, Gerard van; Suur, Marja H.; Neijens, H. J.; Groot, Ronald de

doi:10.1128/iai.65.3.877-881.1997

Cited by 61 publications

(16 citation statements)

References 31 publications

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“…5 are not only in accordance with previous results, but also might give new approach to the mechanisms of adjuvancy of VA-MENGOC-BC 0 . Further studies would be required, but absence of correlation observed years ago between serum antibodies and protective e¤cacy [21], might be explained by more recent ¢nding [22] which, in agreement with our present study, might suggest a concomitant and perhaps more appropriate development of a TH1 immune response.…”

Section: Discussionsupporting

confidence: 86%

Nitric oxide participates in the immune response against Neisseria meningitidis serogroup B

Padrón¹

1999

FEMS Immunology and Medical Microbiology

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The present report explores the role of nitric oxide into the immune response against Neisseria meningitidis serogroup B. Here we show that NO mediates the alphaTNF increase induced by N. meningitidis derived lipopolysaccharides (LPS), at the same time that participates in the bactericidal activity of resting or gammaIFN activated macrophages and plays a role in the specific DTH and IgG response induced by a commercial anti-meningococcal vaccine. Our findings suggest a positive role for NO at the final effector mechanisms and in the early events driving the immunity against N. meningitidis, suggesting also an insight into its role in endotoxic shock.

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Section: Discussionsupporting

confidence: 86%

Nitric oxide participates in the immune response against Neisseria meningitidis serogroup B

Padrón¹

1999

FEMS Immunology and Medical Microbiology

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“…In BM patients, we observed a positive correlation between IDO activity and the inflammatory cytokines IFN-γ and IL-1Ra (Table 2 ). Although each cytokine displays different roles in the inflammation during BM, IFN-γ seems to have a crucial role, mainly during pneumococcal meningitis [ 32 - 35 ], showing to be involved in deleterious proinflammatory effects [ 34 , 35 ]. Concomitantly, KYN metabolites showed a positive correlation with TNF-α and KYNA metabolites with IL-10.…”

Section: Discussionmentioning

confidence: 99%

The kynurenine pathway is involved in bacterial meningitis

Coutinho

Christen

Bellac

et al. 2014

J Neuroinflammation

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BackgroundBacterial meningitis (BM) is characterized by an intense host inflammatory reaction, which contributes to the development of brain damage and neuronal sequelae. Activation of the kynurenine (KYN) pathway (KP) has been reported in various neurological diseases as a consequence of inflammation. Previously, the KP was shown to be activated in animal models of BM, and the association of the SNP AADAT + 401C/T (kynurenine aminotransferase II - KAT II) with the host immune response to BM has been described. The aim of this study was to investigate the involvement of the KP during BM in humans by assessing the concentrations of KYN metabolites in the cerebrospinal fluid (CSF) of BM patients and their relationship with the inflammatory response compared to aseptic meningitis (AM) and non-meningitis (NM) groups.MethodsThe concentrations of tryptophan (TRP), KYN, kynurenic acid (KYNA) and anthranilic acid (AA) were assessed by HPLC from CSF samples of patients hospitalized in the Giselda Trigueiro Hospital in Natal (Rio Grande do Norte, Brazil). The KYN/TRP ratio was used as an index of indoleamine 2,3-dioxygenase (IDO) activity, and cytokines were measured using a multiplex cytokine assay. The KYNA level was also analyzed in relation to AADAT + 401C/T genotypes.ResultsIn CSF from patients with BM, elevated levels of KYN, KYNA, AA, IDO activity and cytokines were observed. The cytokines INF-γ and IL-1Ra showed a positive correlation with IDO activity, and TNF-α and IL-10 were positively correlated with KYN and KYNA, respectively. Furthermore, the highest levels of KYNA were associated with the AADAT + 401 C/T variant allele.ConclusionThis study suggests a downward modulatory effect of the KP on CSF inflammation during BM.

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“…Under physiological conditions almost no endogenous interferon‐γ is detectable in the CNS. In case of CNS inflammation, secretion of interferon‐γ, mainly by infiltrating leukocytes, leads to increased CNS concentrations of this cytokine (Kornelisse et al. 1997).…”

Section: Methodsmentioning

confidence: 99%

Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures

Goos

Lange

Hanisch

et al. 2007

Journal of Neurochemistry

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Toll-like receptors (TLR) play a key role in the recognition of pathogenic organisms. Fibronectin, an extracellular matrix protein, is considered a potent stimulator of the innate immune system through TLR4. In bacterial meningitis, several extracellular matrix proteins and bacterial compounds are elevated in the CSF. For this reason, we hypothesized that these molecules may jointly stimulate the innate immune system and increase neuronal damage in bacterial meningitis. Concentrations of fibronectin were elevated in the CSF of patients suffering from bacterial meningitis, but not in patients with multiple sclerosis, when compared with control patients without CSF abnormalities. In primary cultures of mouse microglial cells, co-administration of fibronectin at concentrations occurring in the CSF in bacterial meningitis (10 microg/mL) with defined TLR agonists [lipopolysaccharide (TLR4), the synthetic lipopeptide tripalmytoyl-cysteinyl-seryl-(lysyl)3-lysine (TLR2) and single-stranded unmethylated cytosine-guanosine oligodesoxynucleotide (TLR9)] led to an additive release of nitric oxide and tumor necrosis factor-alpha when compared with the release elicited by either compound alone. In conclusion, the inflammatory reaction to bacterial compounds can be aggravated by endogenous fibronectin at elevated levels during bacterial CNS infections. This additive or synergistic effect may contribute to neuronal damage during bacterial meningitis.

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Intrathecal production of interleukin-12 and gamma interferon in patients with bacterial meningitis

Cited by 61 publications

References 31 publications

Nitric oxide participates in the immune response against Neisseria meningitidis serogroup B

Nitric oxide participates in the immune response against Neisseria meningitidis serogroup B

The kynurenine pathway is involved in bacterial meningitis

Fibronectin is elevated in the cerebrospinal fluid of patients suffering from bacterial meningitis and enhances inflammation caused by bacterial products in primary mouse microglial cell cultures

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