Cerebrospinal Fluid Levels Of IL-1β Research Articles

Evaluation of neurofilament light chain in the cerebrospinal fluid and blood as a biomarker for neuronal damage in experimental pneumococcal meningitis

BackgroundPneumococcal meningitis (PM) remains a global public health concern and affects all age groups. If acquired during infancy or childhood, permanent neurofunctional deficits including cognitive impairment, cerebral palsy, and secondary epilepsy are typical sequelae of neuronal injury. Determination of patients at risk for the development of brain injury and subsequent neurofunctional sequelae could help to identify patients for focused management. Neurofilament light chain (NfL) is an axonal cytoskeletal protein released upon neuronal injury into the cerebrospinal fluid (CSF) and blood. As little is known about the course of neurofilament release in the course of PM, we measured CSF and serum NfL levels longitudinally in experimental PM (ePM).MethodsEleven-day-old infant Wistar rats were infected intracisternally with Streptococcus pneumoniae and treated with ceftriaxone. At 18 and 42 h post-infection (hpi), the blood and CSF were sampled for NfL measurements by a single molecule array technology. Inflammatory cytokines and MMP-9 in CSF were quantified by magnetic bead multiplex assay (Luminex®) and by gel zymography, respectively.ResultsIn ePM, CSF and serum NfL levels started to increase at 18 hpi and were 26- and 3.5-fold increased, respectively, compared to mock-infected animals at 42 hpi (p < 0.0001). CSF and serum NfL correlated at 18 hpi (p < 0.05, r = 0.4716) and 42 hpi (p < 0.0001, r = 0.8179). Both CSF and serum NfL at 42 hpi strongly correlated with CSF levels of IL-1β, TNF-α, and IL-6 and of MMP-9 depending on their individual kinetics.ConclusionCurrent results demonstrate that during the peak inflammatory phase of ePM, NfL levels in CSF and serum are the highest among CNS disease models studied so far. Given the strong correlation of CSF versus serum NfL, and its CNS-specific signal character, longitudinal measurements to monitor the course of PM could be performed based on blood sample tests, i.e., without the need of repetitive spinal taps. We conclude that NfL in the serum should be evaluated as a biomarker in PM.

Cytokine profiles in cerebrospinal fluid of patients with meningitis at a tertiary general hospital in China.

There has been a great deal of evidence indicating that cytokines participate in meningeal inflammation. Different cytokine profiles may be presented in central nervous system (CNS) infection due to different pathogens. We have attempted to investigate cytokine profiles in cerebrospinal fluid (CSF) of patients with CNS infection. Forty-three patients with CNS infection including tuberculous meningitis, purulent meningitis and cryptococcal meningitis were enrolled and 11 patients with normal CSF were enrolled as control group. The concentrations of Th1-, Th2- and Th17-type cytokines in CSF were detected using multiplex cytokine assay. Furthermore, the correlation between CSF cytokines and CSF parameters in CNS infection was analyzed. The CSF levels of IL-1β, IL-4, IL-6, IL-10, IL-17, IL-23, IL-33, IFN-γ, TNF-α and sCD40L among the patients with CNS infection were all higher than control group (all P<0.05). A remarkable elevation of CSF IL-6 in the patients with CNS infection was observed with the least overlap of the CSF concentrations compared to controls. Moreover, CSF IL-6 levels were strongly negatively correlated with CSF glucose and the CSF/blood glucose ratio (r=-0.4375, P=0.0042; r=-0.4991, P=0.0009). The excessive activation of immune response characterized by elevated levels of CSF Th1-, Th2- and Th17-type cytokines has been observed during CNS infection. Furthermore, we observed negative correlations between CSF IL-6 levels and CSF glucose and CSF/blood glucose ratio in CNS infection. And we suggested that combined CSF IL-6 levels with CSF glucose may serve as a novel biomarker pool for the differential of CNS infection.

Cerebrospinal fluid inflammatory markers in amnestic mild cognitive impairment.

Inflammatory processes might play a significant role at the pathophysiology of Alzheimer's disease (AD). Neuroinflammation is characterized by activation of microglia and the release of inflammatory cytokines, such as interleukin (IL)-1β, IL-6 and tumor necrosis factor-α. Although, it is unknown what the real contribution of these inflammatory markers in the development of AD is. The purpose of the present study was to assess the possible relationship between inflammatory markers in the cerebrospinal fluid (CSF) of amnestic mild cognitive impairment patients (aMCI), aged 60 years or older, and compare with aged healthy controls. We examined concentrations of IL-1β, IL-6 and tumor necrosis factor-α in the CSF of aMCI patients and controls by enzyme immunoassay. aMCI diagnoses were based on anamnesis and Petersen criteria, corroborated by the Clinical Dementia Rating. Cognitive function was assessed by neuropsychological tests. CSF levels of IL-1β (13.735 vs 22.932 pg/mL; P < 0.001) and tumor necrosis factor-α (1.913 vs 2.627 pg/mL; P = 0.002), but not IL-6 (4.178 vs 5.689 pg/mL; P = 0.106), were significantly reduced in the aMCI samples as compared with controls. Individuals with IL-1β < 17 pg/mL were at a 7.2 (CI 1.5-36; P: 0.016) increased odds of aMCI. There was a positive correlation between IL-1β levels and the Consortium to Establish a Registry for Alzheimer's Disease word list score (rs = 0.299; P = 0.046). Linear regression analysis showed that IL-1β levels might explain 13.7% (β = 24.545; P = 0.012) of the variance on this Consortium to Establish a Registry for Alzheimer's Disease subscore. The present results show a pattern of cytokines expression in the CSF of aMCI patients that might be relevant to the pathogeny of prodromal AD. Geriatr Gerontol Int 2017; 17: 239-245.

Silymarin improved 6-OHDA-induced motor impairment in hemi-parkisonian rats: behavioral and molecular study.

BackgroundNeuroinflammation and oxidative stress has been shown to be associated with the development of Parkinson disease (PD). In the present study, we investigated the effect of intraperitoneal (i.p.) administration of silymarin, on 6-OHDA-induced motor-impairment, brain lipid per-oxidation and cerebrospinal fluid (CSF) levels of inflammatory cytokine in the rats.ResultsThe results showed that silymarin is able to improve motor coordination significantly (p < 0.001) in a dose dependent manner. There was a significant (p < 0.001) increase in MDA levels of 6-OHDA-lesioned rats whereas; in silymarin (100, 200 and 300 mg/kg, i.p. for 5 days) pre-treated hemi-parkinsonian rats MDA levels was decreased markedly (p < 0.001). Furthermore the CSF levels of IL-1β was decreased (p < 0.001) in silymarin (100, 200 and 300 mg/kg) pre-treated rats up to the range of normal non-parkinsonian animals.ConclusionWe found that pre-treatment with silymarin could improve 6-OHDA-induced motor imbalance by attenuating brain lipid per-oxidation as well as CSF level of IL-1β as a pro-inflammatory cytokine. We suggest a potential prophylactic effect for silymarin in PD. However, further clinical trial studies should be carried out to prove this hypothesis.

Inflammasome activation mediates inflammation and outcome in humans and mice with pneumococcal meningitis

BackgroundInflammasomes are multi-protein intracellular signaling complexes that have recently been hypothesized to play a role in the regulation of the inflammation response. We studied associations between inflammasome-associated cytokines IL-1β and IL-18 in cerebrospinal fluid (CSF) of patients with bacterial meningitis and clinical outcome, and pneumococcal serotype. In a murine model of pneumococcal meningitis we examined the pathophysiological roles of two inflammasome proteins, NLRP3 (Nod-like receptor protein-3) and adaptor protein ASC (apoptosis-associated speck-like protein).MethodsIn a nationwide prospective cohort study, CSF cytokine levels were measured and related to clinical outcome and pneumococcal serotype. In a murine model of pneumococcal meningitis using Streptococcus pneumoniae serotype 3, we examined bacterial titers, cytokine profiles and brain histology at 6 and 30 hours after inoculation in wild-type (WT), Asc and Nlrp3 deficient mice.ResultsIn patients with bacterial meningitis, CSF levels of inflammasome associated cytokines IL-1β and IL-18 were related to complications, and unfavorable disease outcome. CSF levels of IL-1β were associated with pneumococcal serotype (p<0.001). In our animal model, Asc and Nlrp3 deficient mice had decreased systemic inflammatory responses and bacterial outgrowth as compared to WT mice. Differences between Asc−/− and WT mice appeared sooner after bacterial inoculation and were more widespread (lower pro-inflammatory cytokine levels in both blood and brain homogenate) than in Nlrp3-/-mice. Nlrp3 deficiency was associated with an increase of cerebral neutrophil infiltration and cerebral hemorrhages when compared to WT controls.ConclusionsOur results implicate an important role for inflammasome proteins NLRP3 and ASC in the regulation of the systemic inflammatory response and the development of cerebral damage during pneumococcal meningitis, which may dependent on the pneumococcal serotype.

Changes in Biomarkers Focused on Differences in Disease Course or Treatment in Patients with Neuro-Behçet's Disease

Neurological manifestations of Behçet's disease (NB) are serious complications. However, their pathogenesis remains unclear. The current study examined the levels of proinflammatory cytokines, including IL-1β, IL-6, IL-8 and TNF-α, in cerebrospinal fluid (CSF). CSF cytokines were measured using an enzyme-linked immunosorbent assay. CSF was obtained from 17 patients with acute NB, 19 patients with chronic progressive NB and 20 patients with non-inflammatory neurological diseases, including cerebrovascular disease, cervical spondylosis and degenerative diseases. CSF total cell counts and polymorph nuclear leukocyte counts were significantly lower in the patients with chronic progressive NB than in those with acute NB. The CSF levels of IL-6 and IL-8 were markedly elevated in the NB patients compared with those measured in the control patients. There were no significant differences in the CSF levels of IL-6 and IL-8 between the patients with acute NB and those with chronic progressive NB. In contrast, there were no significant differences in the CSF levels of IL-1β and TNF-α among the control, acute NB and chronic progressive NB patients. Consistently, the CSF levels of IL-6 and IL-8 were significantly decreased following successful treatment in both acute NB and chronic progressive NB patients, whereas the CSF levels of IL-1β and TNF-α were not changed significantly. Of note, the CSF levels of IL-6 were significantly correlated with the CSF levels of IL-8 in the patients with acute NB (r =0.7647, p =0.0003) but not in the patients with chronic progressive NB (r =0.1343, p =0.5835). These results indicate that CSF IL-6 and IL-8 play important roles in the pathogenesis of NB. However, the data also suggest that the mechanisms underlying the elevation of CSF IL-6 and IL-8 might be different in patients with acute NB and those with chronic progressive NB.

Sequential analysis of biomarkers in cerebrospinal fluid and serum during invasive meningococcal disease

The aim of the present study was to determine the profile of different inflammatory molecules in serum and cerebrospinal fluid (CSF) during invasive meningococcal disease (IMD). Their relationship with IMD severity was also assessed. A cohort of 12 patients with IMD was investigated. Paired serum and CSF samples were obtained at the time of diagnostic and follow-up lumbar puncture and were examined using Luminex® analysis. IMD severity correlated with serum interleukin-6 (IL-6) and interleukin-1 receptor antagonist (IL-1ra) on admission. Furthermore, the CSF levels of IL-1β, IL-1ra, IL-6, IL-8, macrophage inflammatory protein-1β (MIP-1β), and monocyte chemoattractant protein-1 (MCP-1) were significantly higher than their respective serum levels. The strongest correlations were found between serum concentrations of IL-1β and IL-1ra, IL-6, IL-8, and MIP-1β, whereas the strongest correlations in CSF were found between endotoxin and IL-8, IL-17, MIP-1β, and MCP-1. As was expected, the concentrations of inflammatory molecules in both serum and CSF significantly decreased after antibiotic treatment. With regard to kinetics, a severe course of IMD correlated positively with rapid declines of CSF IL-6 and cortisol levels. Sequential multiple analyses revealed patterns of inflammatory responses that were associated with the severity of IMD, as well as with the compartmentalization and kinetics of the immune reaction.

Abstract P31: The Central Nervous System’s Inflammatory Cytokine Response to Global Ischemia Due to Cardiac Arrest

Objective: Pro-inflammatory cytokines have been implicated as culprits in neurotoxicity following ischemia in small animal models of stroke. The aim of this study was to measure the central nervous system (CNS) cytokine response following resuscitation from ventricular fibrillation (VF) in a porcine model of cardiac arrest and global hypoxic ischemia. Methods: VF was induced electrically in eleven anesthetized swine. Following seven minutes of untreated VF, animals were resuscitated. Cerebrospinal fluid (CSF) and serum was sampled prior to VF and at 60, 120, and 180 minutes post-resuscitation from which levels of TNF-α IL-1β, and IL-6 were measured. Levels were also drawn in three sham pigs, instrumented but not fibrillated. Results: CSF levels of TNF-α rose following resuscitation (p&lt;0.0001, FIGURE ) and were correlated with CSF levels of IL-1β (Spearman rank correlation r=0.68, p&lt;0.0001) and IL-6 (r=0.55, p=0.0003). Changes in cytokine levels were not observed in sham pigs. Only CSF levels of IL-1β were associated with its serum counterpart (p=0.0006). Conclusions: Measurable increases in pro-inflammatory cytokines in the CSF follow resuscitation from cardiac arrest in this porcine model. The CNS response of all three inflammatory cytokines is highly inter-correlated.

The central nervous system cytokine response to global ischemia following resuscitation from ventricular fibrillation in a porcine model

Pro-inflammatory cytokines have been implicated as culprits in neurotoxicity following ischemia in small animal models of stroke. The aim of this study was to measure the central nervous system (CNS) cytokine response following resuscitation from ventricular fibrillation (VF) in a porcine model of cardiac arrest and global hypoxic ischemia. VF was induced electrically in 11 anesthetized swine. Following 7 min of untreated VF, animals were resuscitated. Cerebrospinal fluid (CSF) and serum was sampled prior to VF and at 60, 120, and 180 min post-resuscitation from which levels of TNF-alpha, IL-1 beta, and IL-6 were measured. Levels were also drawn in three sham pigs, instrumented but not fibrillated. CSF levels of TNF-alpha rose following resuscitation and were associated with CSF levels of IL-1 beta (p=0.0002). CSF levels of all cytokines except TNF-alpha were associated with their serum counterparts. Measurable increases in pro-inflammatory cytokines in the CSF follow resuscitation from cardiac arrest in this porcine model. The CNS response TNF-alpha and IL-1 beta are associated. However, serum levels of TNF-alpha did not seem to predict CSF levels in this study, consistent with the concept of immune privilege of the CNS.

Increased intrathecal inflammatory activity in frontotemporal dementia: pathophysiological implications

Objective: Immunological mechanisms may be part of the pathophysiological mechanisms in frontotemporal dementia (FTD), but hitherto only vague evidence of such mechanisms has been presented. The aim of this study...

Plasma and cerebrospinal fluid interleukin-1 beta and interleukin-6 in hospitalized schizophrenic patients.

Interleukin (IL)-1 beta and IL-6 levels in plasma and cerebrospinal fluid (CSF) of 14 medicated schizophrenic patients and 9 controls were measured by enzyme-linked immunosorbent assay. Almost no detectable levels of IL-6 in plasma or CSF from patients or controls were found. With regard to mean plasma or CSF levels of IL-1 beta there were no statistically significant differences between the two groups investigated. The dose of neuroleptic medication the patients used did not correlate with the IL-1 beta plasma levels. For the whole series of subjects (n = 23) or for the schizophrenic patients (n = 14) no correlation between the plasma and CSF levels of IL-1 beta was found.