Divergent cerebrospinal fluid cytokine network induced by non-viral and different viral infections on the central nervous system

Abstract

BackgroundMeningoencephalitis is one of the most common disorders of the central nervous system (CNS) worldwide. Viral meningoencephalitis differs from bacterial meningitis in several aspects. In some developing countries, bacterial meningitis has appropriate clinical management and chemotherapy is available. Virus-associated and virus not detected meningoencephalitis are treatable, however, they may cause death in a few cases. The knowledge of how mediators of inflammation can induce disease would contribute for the design of affordable therapeutic strategies, as well as to the diagnosis of virus not detected and viral meningoencephalitis. Cytokine-induced inflammation to CNS requires several factors that are not fully understood yet.MethodsConsidering this, several cytokines were measured in the cerebrospinal fluid (CSF) of patients with undiagnosed and viral meningoencephalitis, and these were correlated with cellularity in the CSF.ResultsThe results demonstrate that an altered biochemical profile alongside increased cellularity in the cerebrospinal fluid is a feature of patients with meningoencephalitis that are not associated with the detection of virus in the CNS (P < 0.05). Moreover, HIV-positive patients (n = 10) that evolve with meningoencephalitis display a distinct biochemical/cytological profile (P < 0.05) in the cerebrospinal fluid. Meningoencephalitis brings about a prominent intrathecal cytokine storm regardless of the detection of virus as presumable etiological agent. In the case of Enterovirus infection (n = 13), meningoencephalitis elicits robust intrathecal pro-inflammatory cytokine pattern and elevated cellularity when compared to herpesvirus (n = 15) and Arbovirus (n = 5) viral infections (P < 0.05).ConclusionDifferences in the cytokine profile of the CSF may be unique if distinct, viral or presumably non-viral pathways initially trigger the inflammatory response in the CNS.

Cytokine characteristic of cerebrospinal fluid from children with enteroviral meningitis compared to bacterial meningitis

“…Even cytokines seemed to have the ability to distinguish enterovirus infection from other viruses. Enterovirus meningoencephalitis group showed higher level of CSF IL‐6, TNF, and IL‐17 when compared to arbovirus, lentivirus, and herpes groups . While compared to patients with human parechovirus meningitis, CSF levels of the majority cytokines were still significantly higher in patients with EVM …”

Advances in Biomarker-Guided Therapy for Pediatric- and Adult-Onset Neuroinflammatory Disorders: Targeting Chemokines/Cytokines

“…CSF CXCL8, CXCL9, and CXCL10 are elevated in herpes simplex herpes simplex virus (HSV) 1 encephalitis and HSV2 meningitis, whereas CXCL11 and CCL8 are elevated in HSV2 meningitis alone ( 151 ). Among viral CNS meningoencephalitides, enterovirus and lentivirus have comparably higher CSF IL-12 and IFN-γ concentrations, whereas arbovirus is associated with lower CSF cytokine concentrations than other viral etiologies ( 168 ). In mumps meningitis in children, the concentrations of CSF CXCL8, IL-10, IL-12, IL-13, and IFN-γ were higher than in other viral meningitides ( 153 ).…”

Sequential transmigration of polymorphonuclear cells and naive CD3 + T lymphocytes across the blood-cerebrospinal-fluid barrier in vitro following infection with Echovirus 30

“…Due to the ability of the virus to spread and infect other host organs, the initial silent infection may quickly develop more negative effects. [57][58][59][60]. Further investigations showed that even IL-6 and TNF-α, which are usually more linked to bacterial meningitis, are present in the CNS during an aseptic viral meningitis [61].…”