Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae

Perdomo‐Celis, Federico; Torres, Miguel A.; Ostos, Henry; Gutiérrez-Achury, Javier; Molano, V J C; Durán, Luis Fernando; González, Guillermo; Narváez, Carlos F.

doi:10.4137/bmi.s35005

Cited by 15 publications

(18 citation statements)

References 57 publications

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“…These results were more recently supported when it was found that in patients with non-meningitis related sepsis, not only were cytokine levels higher in the CSF than in plasma, but also levels of CSF IL-6, IL-8, IL-10, IL-1β, and TNF-a, and plasma IL-10 and IL-12p70 were significantly higher in patients with severe sepsis than in those with sepsis [36].…”

Section: Clinical Effects Of Inflammatory Cytokinesmentioning

confidence: 78%

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Acute bacterial meningitis and stroke

Siegel

2019

Neurol Neurochir Pol.

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Introduction. Acute bacterial meningitis remains a common disease, especially in developing countries. Although advances over the last century have improved mortality and morbidity, the neurological adverse effects remain high. Specifically, acute ischaemic stroke is a serious comorbidity that represents both disease severity and poor prognosis. This review presents the clinical connection between meningitis and stroke, and discusses the neuroinflammatory components that have direct ties between these diseases. State of the art. Ischaemic stroke is the direct result of the inflammatory response produced to eradicate infectious pathogens. Bacterial virulence factors and pathogen-associated molecular patterns cause direct damage to the blood-brain barrier and trigger leukocytes to react to the infection. Cytokines are released that cause further destruction of the blood-brain barrier, lead to neuronal death, and recruit the prothrombotic effects of the coagulation cascade through the complement system. Unfortunately, this inflammatory response causes vasculopathy and hypercoagulation of the cerebral blood vessels, leading to cerebral ischaemia. Clinical implications. Pharmacological attempts to mitigate this inflammatory response have produced both positive and negative results. On the one hand, corticosteroids have been shown to improve mortality if given early in patients with bacterial meningitis, particularly pneumococcal meningitis. On the other hand, corticosteroids have been linked to delayed cerebral infarction and other adverse effects. Future directions. New targets for specific inflammatory markers have shown success in rodent models, but have not yet been proven beneficial in humans. Genetic markers are on the horizon, and may serve as individualised targets for diagnosis and therapy.

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Section: Clinical Effects Of Inflammatory Cytokinesmentioning

confidence: 78%

“…Jason L. Siegel, Acute bacterial meningitis and stroke Additionally, higher CSF levels of IL-6 and IL-12p70 were correlated with worse long-term outcomes [36].…”

Section: Clinical Effects Of Inflammatory Cytokinesmentioning

confidence: 99%

Acute bacterial meningitis and stroke

Siegel

2019

Neurol Neurochir Pol.

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“…This increase was not noted in the plasma from the same patient. We have described that after bacterial infection of the human meninges, a massive proinflammatory cytokine response occurs selectively in the CSF but not blood, and the magnitude of this response is correlated with the clinical severity and development of sequelae (Perdomo-Celis et al, 2015). Other neurotropic viruses such as herpes viruses are also known to induce the selective expression of IL-6 and IFN-g intrathecally after infection (Aurelius et al, 1994).…”

Section: Discussionmentioning

confidence: 99%

Clinical, laboratory and immune aspects of Zika virus-associated encephalitis in children

Salgado

Vega

Rodríguez

et al. 2020

International Journal of Infectious Diseases

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To evaluate the clinical, laboratory, and immune characteristics of Zika virus (ZIKV)-associated encephalitis in pediatric patients after the epidemic in Huila, southern Colombia. Methods: A pediatric neuro-surveillance hospital study was conducted in a referral health center in southern Colombia, from October 2016 to October 2017. Cases of encephalitis were confirmed by nucleic acid amplification tests and serological methods in cerebrospinal fluid (CSF), plasma, and/or urine. Levels of six cytokines were evaluated by flow cytometry. Patients underwent daily clinical and laboratory follow-up. Results: Twenty children with probable encephalitis were included for further studies and 16 of them were confirmed. Four cases of bacterial meningoencephalitis (Streptococcus pneumoniae, group B Streptococcus, Staphylococcus epidermidis, and Escherichia coli) and 12 cases of viral encephalitis were identified, six of them associated with ZIKV infection. Other viral encephalitis cases were caused by herpes viruses (n = 3), enterovirus (n = 2), and dengue virus type 2 (DENV-2; n = 1) infections. ZIKVassociated encephalitis symptoms subsided faster than those of patients with encephalitis caused by other agents. CSF analysis revealed lymphocytic pleocytosis. Compared to healthy controls, children with ZIKV-associated encephalitis presented modest plasma interleukin (IL)-10 but not IL-2, IL-4, IL-6, interferon gamma (IFN-g), or tumor necrosis factor alpha (TNF-α). Cytokine expression was differentially regulated, as dramatically elevated IL-6, IL-10, and IFN-g levels were observed in CSF but not in paired plasma samples in one of the patients with ZIKV detectable in CSF. Conclusions: This study provides evidence that ZIKV is responsible for pediatric encephalitis in endemic areas, and the local presence of the virus may induce cephalic but not systemic expression of cytokines.

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“…1,2 Immune-regulatory mechanisms in meningitis have been extensively investigated in small animal models 3, 4 and through correlative studies of body fluids in patients demonstrating a pleiotropic cytokine response. [5][6][7][8][9] To date, no individual cytokine or other endogenous immune regulator has been found to be sufficient for inducing fatal meningitis.…”

Section: Introductionmentioning

confidence: 99%

“…A prominent new agent under development as an investigational new drug (IND) is interleukin-10 (IL-10), a cytokine most often classified as anti-inflammatory, which can be detected in the nervous system of patients with meningitis 7,8 and (used as a therapeutic) is a candidate for treating a variety of CNS disorders such as multiple sclerosis and neuropathic pain. 10 In the case of analgesic testing of IL-10, gene vectors are used to deliver the cytokine to the intrathecal (i.t.)…”

Section: Introductionmentioning

confidence: 99%

Fatal Meningitis in Swine after Intrathecal Administration of Adeno-associated Virus Expressing Syngeneic Interleukin-10

et al. 2017

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Interleukin-10 (IL-10) delivered by intrathecal (i.t.) gene vectors is a candidate investigational new drug (IND) for several chronic neurological disorders such as neuropathic pain. We performed a preclinical safety study of IL-10. A syngeneic large animal model was used delivering porcine IL-10 (pIL-10) to the i.t. space in swine by adeno-associated virus serotype 8 (AAV8), a gene vector that was previously found to be nontoxic in the i.t. space. Unexpectedly, animals became ill, developing ataxia, seizures, and an inability to feed and drink, and required euthanasia. Necropsy demonstrated lymphocytic meningitis without evidence of infection in the presence of normal laboratory findings for body fluids and normal histopathology of peripheral organs. Results were replicated in a second animal cohort by a team of independent experimenters. An extensive infectious disease and neuropathology workup consisting of comprehensive testing of tissues and body fluids in a specialized research veterinary pathology environment did not identify a pathogen. These observations raise the concern that i.t. IL-10 therapy may not be benign, that previously used xenogeneic models testing the human homolog of IL-10 may not have been sensitive enough to detect toxicity, and that additional preclinical studies may be needed before clinical testing of IL-10 can be considered.

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Patterns of Local and Systemic Cytokines in Bacterial Meningitis and its Relation with Severity and Long-Term Sequelae

Cited by 15 publications

References 57 publications

Acute bacterial meningitis and stroke

Acute bacterial meningitis and stroke

Clinical, laboratory and immune aspects of Zika virus-associated encephalitis in children

Fatal Meningitis in Swine after Intrathecal Administration of Adeno-associated Virus Expressing Syngeneic Interleukin-10

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