The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis.

Saukkonen, Kirsi; Sande, Stephen; Cioffe, C; Wolpe, Stephen D.; Sherry, Barbara; Cerami, Anthony; Tuomanen, Elaine

doi:10.1084/jem.171.2.439

Cited by 348 publications

(215 citation statements)

References 30 publications

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“…IL-1 and TNF-␣ display synergistic actions and stimulate the release of each other, thereby amplifying the cascade of other inflammatory mediators (54). A high level of TNF-␣ and IL-1 is found in the CSF of patients suffering from bacterial meningitis and experimental bacterial meningitis (55). Also, in case of CpG ODN-triggered meningitis, the levels of intrathecal TNF-␣ were clearly elevated.…”

Section: Discussionmentioning

confidence: 83%

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

Deng

Liu

Tarkowski

2001

The Journal of Immunology

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Unmethylated CpG motifs are frequently found in bacterial DNA, and have recently been shown to exert immunostimulatory effects on leukocytes. Since bacterial infections in the CNS will lead to local release of prokaryotic DNA, we wanted to investigate whether such an event might trigger meningitis. To that end, we have intracisternally injected mice and rats with bacterial DNA and oligonucleotides containing CpG motifs. Histopathological signs of meningitis were evident within 12 h and lasted for at least 14 days, and were characterized by an influx of monocytic, Mac-3+ cells and by a lack of T lymphocytes. To study the mechanisms whereby unmethylated CpG DNA gives rise to meningitis, we deleted the monocyte/macrophage population leading to abrogation of brain inflammation. Also, interaction with NF-κB using antisense technology led to down-regulation of proinflammatory cytokine production and frequency of meningitis. Furthermore, specific interactions with vascular selectin expression and inhibition of NO synthase led to a significant amelioration of meningitis, altogether indicating that this condition is dependent on macrophages and their products. In contrast, neutrophils, NK cells, T/B lymphocytes, IL-12, and complement system were not instrumental in meningitis triggered by bacterial DNA containing CpG motifs. This study proves that bacterial DNA containing unmethylated CpG motifs induces meningitis, and indicates that this condition is mediated in vivo by activated macrophages.

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Section: Discussionmentioning

confidence: 83%

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

Deng

Liu

Tarkowski

2001

The Journal of Immunology

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“…IL-1β has potent stimulatory effects on granulocytes white cells; it promotes the adhesion of neutrophils and monocytes in endothelial cells 33 . IL-1β is found in the CSF of patients with bacterial meningitis 34 , furthermore, in animal models it was produced in the first 24 h after pneumococcal meningitis induction 30 , although intrathecal administration of IL-1β did not lead to CSF pleocytosis or brain edema 35 . However, the mortality was significantly higher and earlier in the course of the disease among IL-1 receptor (IL-1R) gene-deficient mice, demonstrating that endogenous IL-1β is required for an adequate host defense in pneumococcal meningitis 36 .…”

Section: Inflammation Cytokinesmentioning

confidence: 99%

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Barichello

Generoso

Collodel

et al. 2012

Arq. Neuro-Psiquiatr.

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Pneumococcal meningitis is a life-threatening disease characterized by an acute purulent infection affecting piamater, arachnoid and the subarachnoid space. The intense inflammatory host's response is potentially fatal and contributes to the neurological sequelae. Streptococcus pneumoniae colonizes the nasopharynx, followed by bacteremia, microbial invasion and blood-brain barrier traversal. S. pneumoniae is recognized by antigen-presenting cells through the binding of Toll-like receptors inducing the activation of factor nuclear kappa B or mitogen-activated protein kinase pathways and subsequent up-regulation of lymphocyte populations and expression of numerous proteins involved in inflammation and immune response. Many brain cells can produce cytokines, chemokines and others pro-inflammatory molecules in response to bacteria stimuli, as consequence, polymorphonuclear are attracted, activated and released in large amounts of superoxide anion and nitric oxide, leading to the peroxynitrite formation, generating oxidative stress. This cascade leads to lipid peroxidation, mitochondrial damage, blood-brain barrier breakdown contributing to cell injury during pneumococcal meningitis.

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“…TGF-b together with the antiinflammatory cytokines may down-modulate the proinflammatory cytokines IFN-g and TNF-a. Both IFN-g and TNF-a are known to mediate inflammatory reactions in the CNS [2,19,20]. The induction of anti-TGF-b and anti-IL-10 Aabs, but not IL-4 (see above), may then follow in order to down-regulate the increased induction of these cytokines, thereby preventing their adverse immunosuppressive effects.…”

Section: Discussionmentioning

confidence: 99%

Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis

Bakhiet¹,

Mustafa²,

Zhu³

et al. 1998

Clinical and Experimental Immunology

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SUMMARYWe have recently described the induction of anti-cytokine autoantibodies (Aabs) in the serum as a novel mechanism for cytokine regulation during bacterial infections. Here we use the infant rat-model of Haemophilus influenzae type b (Hib) meningitis to examine the induction of five potentially important cytokines and their autoantibody responses in the CSF. Protein levels of the cytokines interferon-gamma (IFN-g), tumour necrosis factor-alpha (TNF-a), transforming growth factor-beta (TGF-b), IL-4 and IL-10 were detected at day 3 post-inoculation (p.i.) with maximum induction at day 8. Thereafter, these levels of cytokines had become undetectable. Increased Aab titres to these cytokines, except IL-4, were registered with peak levels between days 7 and 9. Upon re-inoculation with Hib at day 30, regeneration of Aabs was recorded 7 days later (i.e. at day 37). To control the specificity of these Aabs, preincubation of the CSF with a cytokine inhibited the binding effects of that particular cytokine, but not those of any other cytokine. Aabs dose-dependently inhibited IFN-g-induced MHC expression by peritoneal macrophages and TNF-a-mediated L929 cytotoxicity. Our data demonstrate for the first time the existence of the anti-cytokine antibodies in the CSF of the meningitis Hib model. Furthermore, the data present a role for the Aabs in cytokine regulation, which is consistent with the previously demonstrated effects of the Aabs in the serum.

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The role of cytokines in the generation of inflammation and tissue damage in experimental gram-positive meningitis.

Cited by 348 publications

References 30 publications

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

Intracisternally Localized Bacterial DNA Containing CpG Motifs Induces Meningitis

Pathophysiology of acute meningitis caused by Streptococcus pneumoniae and adjunctive therapy approaches

Induction of cytokines and anti-cytokine autoantibodies in cerebrospinal fluid (CSF) during experimental bacterial meningitis

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