interleukin-8 and Meningitis--Bacterial

Bacterial meningitis is the serious infection of the central nervous system (CNS), and stimulated by bacteria inflammatory host response has crucial role in its pathogenesis. The most important elements of this response are cytokines, especially tumor necrosis factor (TNF-alpha), interleukin-1 beta (IL-1 beta), interleukin-6 (IL-6), interleukin-8 (IL-8), and interleukin-10 (IL-10), which have antiinflammatory activity. Production of cytokines in the CNS triggers a cascade of inflammatory mediators. Better understanding of mechanisms which take place during the course of the bacterial meningitis can be useful in differential diagnosis, prognosis and treatment of this disease. Investigations on the role of cytokines in the bacterial meningitis, have great therapeutic implications, and can result in introduction to the treatment antiinflammatory drugs, which can help to reduce mortality rate and number of complications.

Topics: Anti-Inflammatory Agents; Cytokines; Humans; Interleukin-1; Interleukin-10; Interleukin-6; Interleukin-8; Meningitis, Bacterial; Tumor Necrosis Factor-alpha

Topics: Biomarkers; Brain Injuries; Humans; Interleukin-8; Meningitis, Bacterial; Prognosis

Despite of antimicrobial therapy mortality rate in the bacterial meningitis (BM) is high. The aim of the study was to assess the influence of anti-inflammatory treatment with dexamethasone and dexamethasone with pentoxifylline on the course of this disease and concentration of proinflammatory cytokines TNF-alpha, IL-1 beta, II-8 in the cerebrospinal fluid (CSF). 42 patients with the BM were analysed. They were divided into three groups on the basis of applied therapy: A--treated only with antibiotics, A+D--treated with antibiotics and dexamethasone, A+D+P--treated with antibiotics, dexamethasone and pentoxifylline. Anti-inflammatory therapy did not have impact on the resolution of inflammation (pleocytosis, protein and glucose level) in the CSF. However, it was established that adjuvant treatment with dexa-methasone and pentoxifylline has beneficial effect on the course of the BM. In this group 61.5% of patients recovered, in comparison with 28.6% in the group A+D and 26.7% in the group A. Mortality rate was: in the group A--33%, A+D--21.4%, A+D+P--7.7% (p = 0.01). Correlation between the outcome of the BM in the investigated groups and cytokines concentration in CSF was observed. In the group A+D+P all patients responded to the therapy with decrease of cytokine concentration, and coefficients of variation were low (TNF-alpha--1%, IL-1 beta--23.6%, IL-8--18.9%). Also in the group A+D decrease of cytokines concentration in the CSF was observed, however was not such significant in all cases. In the group of patients treated only with antibiotics concentration of cytokines in the CSF varied, even increased in some of them. Our investigation indicates that inhibition of cytokines production in central nervous system (CNS) with dexamethasone and pentoxifylline improves the outcome of BM and is associated with the reduction of neurological sequels and deaths.

Topics: Adult; Aged; Aged, 80 and over; Anti-Bacterial Agents; Anti-Inflammatory Agents; Dexamethasone; Drug Therapy, Combination; Female; Humans; Interleukin-1; Interleukin-8; Male; Meningitis, Bacterial; Middle Aged; Pentoxifylline; Treatment Outcome; Tumor Necrosis Factor-alpha

Bacterial meningitis is a life-threatening disease with high mortality and common long-term sequelae. The inflammatory response in the subarachnoid space, modulated by different cytokines, plays a major role in the pathogenesis of acute central nervous system infections. We aimed to examine correlations of interleukin (IL)-6, IL-8, IL-10, IL-12(p40), and tumor necrosis factor (TNF)-α levels with disease severity, complications, and outcome in patients with acute bacterial meningitis.. The study involved 30 patients with bacterial meningitis/meningoencephalitis admitted to the University Hospital St. George, Plovdiv over a period of 4 years. Patients were selected based on clinical presentation and laboratory abnormalities, consistent with a neuroinfection. Enzyme-linked immunosorbent assay was used to measure the studied cytokines in both cerebrospinal fluid (CSF) and serum in parallel. For microbiological diagnosis multiplex, polymerase chain reaction, and CSF culture were used.. In patients with acute bacterial meningitis CSF levels of IL-6, IL-8, IL-10, and TNF-α are significantly increased than in serum. CSF TNF-α, CSF IL-8, and CSF IL-10 had a moderate negative correlation to CSF glucose. It was found that serum IL-8 is significantly elevated in patients who experienced neurological complications, have severe clinical course, and in deceased patients. CSF IL-10 is increased only in patients with severe acute bacterial meningitis.. Among patients with acute bacterial meningitis serum IL-8 could delineate these with increased risk of neurological complications, severe clinical course, and fatal outcome. Serum IL-8 and CSF IL-10 could be used as indicators of disease severity.

Topics: Cytokines; Disease Progression; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Meningitis, Bacterial; Nervous System Diseases; Tumor Necrosis Factor-alpha

The differential diagnosis between postneurosurgical bacterial meningitis and aseptic meningitis remains challenging both for the clinician and the laboratory. Combinations of markers, as opposed to single ones, may improve diagnosis and thereby survival.. This prospective cohort study included patients with suspected bacterial meningitis after neurosurgery. The patients were divided into two groups according to the diagnostic criteria of meningitis involving a postneurosurgical bacterial meningitis group and a postneurosurgical aseptic meningitis group. Four biomarkers, including cerebrospinal fluid procalcitonin, lactate, interleukin-8 and interleukin-10 were assayed separately, and three algorithms were constructed using a linear combination. The area under the receiver operating characteristic curve was used to compare their performances.. A cohort of 112 patients was enrolled in our study. Forty-three patients were diagnosed with postneurosurgical bacterial meningitis, and the cerebrospinal fluid values of their biomarkers were higher in patients with postneurosurgical bacterial meningitis than with postneurosurgical aseptic meningitis. The area under the receiver operating characteristic curves for the detection of postneurosurgical bacterial meningitis were 0.803 (95% confidence interval [CI], 0.724-0.883) for procalcitonin; 0.936 (95% CI, 0.895-0.977) for lactate; 0.771 (95% CI, 0.683-0.860) for interleukin-8; 0.860 (95% CI, 0.797-0.929) for interleukin-10; 0.937 (95% CI, 0.897-0.977) for the composite two-marker test; 0.945 (95% CI, 0.908-0.982) for the composite three-marker test and 0.954 (95% CI, 0.922-0.989) for the composite of all tests. The area under the receiver operating characteristic curves of the combination tests were greater than those of the single markers.. Combining information from several markers improved the diagnostic accuracy in detecting postneurosurgical bacterial meningitis.

Topics: Adult; Biomarkers; China; Cohort Studies; Diagnosis, Differential; Female; Humans; Interleukin-10; Interleukin-8; Lactic Acid; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Procalcitonin; Prospective Studies

Meningitis necessitates immediate diagnosis and therapy. It is important to distingu- ish bacterial from aseptic meningitis, as this help to avoid complications and unnece- ssary antibiotic use. This work assessed the diagnostic and prognostic role of cerebro-spinal fluid interleukin-8 (IL-8) level in adult patients with meningitis. Ninety adult patients with meningitis were studied. They were divided into 3 groups: bacterial, tuberculous and aseptic meningitis. Full clinical examination and laboratory workup of meningitis were done. Cerebrospinal fluid (CSF) IL-8 levels were assessed. Patients were followed up till discharge or death. CSF IL-8 level was significantly higher in bacterial and tuberculous meningitis in comparison to aseptic meningitis. At cut off value 121.77 pg/ml, the area under ROC curve was 0.774 with efficacy 69% for differentiating viral from non-viral meningitis. The test efficacy is low in differentiating tuberculous from bactedal meningitis. There is no correlation of CSF IL-8 levels and disease severity or prognosis.

Topics: Adult; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Haemophilus influenzae; Humans; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Meningitis, Haemophilus; Meningitis, Meningococcal; Meningitis, Pneumococcal; Middle Aged; Neisseria meningitidis; Prognosis; ROC Curve; Streptococcus pneumoniae; Tuberculosis, Meningeal

The objective of the present study was to determine whether selective inflammatory cytokine concentrations within cerebrospinal fluid are useful markers for the differential diagnosis of aseptic and bacterial meningitis within neurosurgical patients.. Prospective, open-label, observational, cohort study.. Neurosurgical ICU, Chang Gung Memorial Hospital.. Thirty-two consecutive neurosurgical patients who had postoperative fever following external ventricular drain insertion for the treatment of brain injury underwent serial cerebrospinal fluid cytokine analysis pre and post fever to determine the value of such markers in ascertaining the differential diagnosis of meningitis.. Cerebrospinal fluid samples were collected on the day of fever onset, as well as on day 2 and 4 pre and post fever development. Tumor necrosis factor-α, interleukin-1β, interleukin-6, interleukin-8, transforming growth factor-β, and procalcitonin were subsequently analyzed using enzyme-linked immunosorbent assay analysis techniques.. Inflammatory marker levels were compared among febrile aseptic, bacterial, and nonmeningitis patients to determine cerebrospinal fluid inflammatory changes over time. Significant increases in cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, interleukin-6, and interleukin-8 levels were observed within patients with bacterial meningitis at fever onset, which was not evident in aseptic or nonmeningitis patients. Furthermore, significant increases in cerebrospinal fluid tumor necrosis factor-α, interleukin-1β, interleukin-6, and interleukin-8 levels were detected as early as 4 days prior to fever onset within patients with bacterial meningitis when compared with both aseptic and nonmeningitis groups. Interestingly, procalcitonin was only significantly increased in patients with bacterial meningitis on the fourth day post fever.. The present study suggests that raised cerebrospinal fluid tumor necrosis factor -α, interleukin-1β, and interleukin-8 in a temporal manner may indicate early bacterial meningitis development in neurosurgical patients, enabling earlier diagnostic certainty and improved patient outcomes.

Topics: Adult; Aged; Area Under Curve; Calcitonin; Calcitonin Gene-Related Peptide; Cohort Studies; Cytokines; Diagnosis, Differential; Enzyme-Linked Immunosorbent Assay; Female; Fever; Humans; Inflammation Mediators; Interleukin-6; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Prognosis; Prospective Studies; Protein Precursors; Risk Assessment; ROC Curve; Survival Rate; Tumor Necrosis Factor-alpha

Bacterial meningitis (BM) is an infectious disease that results in high mortality and morbidity. Despite efficacious antibiotic therapy, neurological sequelae are often observed in patients after disease. Currently, the main challenge in BM treatment is to develop adjuvant therapies that reduce the occurrence of sequelae. In recent papers published by our group, we described the associations between the single nucleotide polymorphisms (SNPs) AADAT +401C > T, APEX1 Asn148Glu, OGG1 Ser326Cys and PARP1 Val762Ala and BM. In this study, we analyzed the associations between the SNPs TNF -308G > A, TNF -857C > T, IL-8 -251A > T and BM and investigated gene-gene interactions, including the SNPs that we published previously.. The study was conducted with 54 BM patients and 110 healthy volunteers (as the control group). The genotypes were investigated via primer-introduced restriction analysis-polymerase chain reaction (PIRA-PCR) or polymerase chain reaction-based restriction fragment length polymorphism (PCR-RFLP) analysis. Allelic and genotypic frequencies were also associated with cytokine and chemokine levels, as measured with the x-MAP method, and cell counts. We analyzed gene-gene interactions among SNPs using the generalized multifactor dimensionality reduction (GMDR) method.. We did not find significant association between the SNPs TNF -857C > T and IL-8 -251A > T and the disease. However, a higher frequency of the variant allele TNF -308A was observed in the control group, associated with changes in cytokine levels compared to individuals with wild type genotypes, suggesting a possible protective role. In addition, combined inter-gene interaction analysis indicated a significant association between certain genotypes and BM, mainly involving the alleles APEX1 148Glu, IL8 -251 T and AADAT +401 T. These genotypic combinations were shown to affect cyto/chemokine levels and cell counts in CSF samples from BM patients.. In conclusion, this study revealed a significant association between genetic variability and altered inflammatory responses, involving important pathways that are activated during BM. This knowledge may be useful for a better understanding of BM pathogenesis and the development of new therapeutic approaches.

Topics: Brazil; Female; Gene Frequency; Humans; Inflammation; Interleukin-8; Male; Meningitis, Bacterial; Odds Ratio; Polymerase Chain Reaction; Polymorphism, Restriction Fragment Length; Polymorphism, Single Nucleotide; Statistics, Nonparametric; Tumor Necrosis Factor-alpha

We evaluated the levels of cerebrospinal fluid concentrations of tumor necrosis factor-α, interleukin-6, and interleukin-8 in bacterial meningitis in children.. The study included children up to 14 years of age admitted to a pediatric ward with fever, headache, vomiting, and seizures. The diagnosis of bacterial meningitis was based on clinical features: physical examination, blood and cerebrospinal fluid cytochemical findings, Gram stain, and bacterial culture. The cerebrospinal fluid levels of tumor necrosis factor-α, interleukin-6, and interleukin-8 were measured in 57 children with bacterial meningitis, 15 with viral meningitis, and 15 controls by enzyme-linked immunosorbent assay methods.. The mean concentrations of cerebrospinal fluid, tumor necrosis factor-α, interleukin-6, and interleukin-8 were 1108 ± 183, 652 ± 287, and 442 ± 120 pg/mL, respectively, in children with bacterial meningitis and were significantly increased in those in the viral meningitis group (tumor necrosis factor-α : 711 ± 105, IL-6 : 272 ± 161, IL-8 : 175 ± 62 pg/mL; P < 0.001) or control (390 ± 37, 59 ± 17, 19 ± 13 pg/mL, respectively, P < 0.001). At optimum cutoff level based on the receiver operating characteristic curve, cerebrospinal fluid cytokines (tumor necrosis factor-α, interleukin-6, and interleukin-8) showed sensitivity and specificity of 100% for the diagnosis of bacterial meningitis. For differentiation of bacterial from viral meningitis, cerebrospinal fluid level of tumor necrosis factor-α, IL-6, and IL-8 showed sensitivity and specificity of 94.7% and 86.7%, 80.7% and 53.3%, and 89.5% and 86.7%, respectively.. The increased concentration of cerebrospinal fluid tumor necrosis factor-α, interleukin-6, and interleukin-8 in children with meningitis suggests a role in the pathogenesis of bacterial meningitis and these levels might prove to be useful in children whose diagnosis is in question.

Topics: Adolescent; Child; Child, Preschool; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-6; Interleukin-8; Male; Meningitis, Bacterial; Predictive Value of Tests; ROC Curve; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

No doubt, the distinguishing between bacterial and aseptic meningitis in the emergency department could help to limit unnecessary antibiotic use and hospital admissions. This study evaluated the role of cerebrospinal fluid IL-8 in differentiating acute bacterial meningitis (ABM) from aseptic meningitis (AM). A total of 80 hospitalized patients with clinical presentations of suspected acute meningitis were subjected to estimation of IL-8 CSF concentrations. The results showed that CSF IL-8 levels were higher in acute bacterial meningitis than in aseptic ones (p < 0.05). The best cut-off value of CSF IL8 for early diagnosis of bacterial meningitis was 3.6 ng/ml with a sensitivity of 82.5% and a specificity of 85.0%.

Topics: Adolescent; Adult; Biomarkers; Female; Humans; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Young Adult

Interactions between commensal pathogens and hosts are critical for disease development but the underlying mechanisms for switching between the commensal and virulent states are unknown. We show that the human pathogen Neisseria meningitidis, the leading cause of pyogenic meningitis, can modulate gene expression via uptake of host pro-inflammatory cytokines leading to increased virulence. This uptake is mediated by type IV pili (Tfp) and reliant on the PilT ATPase activity. Two Tfp subunits, PilE and PilQ, are identified as the ligands for TNF-α and IL-8 in a glycan-dependent manner, and their deletion results in decreased virulence and increased survival in a mouse model. We propose a novel mechanism by which pathogens use the twitching motility mode of the Tfp machinery for sensing and importing host elicitors, aligning with the inflamed environment and switching to the virulent state.

Topics: Animals; Bacterial Proteins; Chromatin Immunoprecipitation; Cytokines; Disease Models, Animal; DNA-Binding Proteins; Fimbriae Proteins; Fimbriae, Bacterial; Gene Expression Regulation, Bacterial; Genome, Bacterial; Humans; Interleukin-8; Ligands; Meningitis, Bacterial; Mice; Mice, Transgenic; Neisseria meningitidis; Tumor Necrosis Factor-alpha; Virulence; Virulence Factors

In several cases of meningitis routinely used diagnostic procedures are unable to identify the cause of this disease. The objective of the present study was to determine whether proinflammatory cytokine (tumour necrosis factor (TNF-α), interleukin-1β (IL-1β), interleukin-8 (IL-8)) and nitric oxide (NO) concentrations in the CSF are useful markers for the differential diagnosis of meningitis.. Sixty-seven patients (42 patients with bacterial meningitis and 25 patients with viral meningitis) were included in the present study. In the investigated group, the TNF-α, IL-1β and IL-8 concentrations in the CSF samples collected on the day of admission were assessed. Furthermore, the NO concentrations were assessed in 23 patients.. The results revealed that the measurement of proinflammatory cytokines in CSF can aid in a differential diagnosis. In particular, a high concentration of TNF-α may be a sensitive and specific marker of a bacterial aetiology of the neuroinfection. In the present study, TNF-α concentrations greater than 75.8 pg/ml differentiated between bacterial and viral meningitis with 100% sensitivity and specificity. The NO concentration in the CSF was also significantly greater in patients with bacterial meningitis than in those with viral meningitis.. The assessment of TNF-α, IL-1β and IL-8 concentrations in the CSF is useful in the differential diagnosis of neuroinfection. Because many factors may influence NO production in the central nervous system (CNS), it is not clear whether NO values can be used for the differential diagnosis of meningitis, and further studies are required.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cerebrospinal Fluid; Cytokines; Female; Humans; Interleukin-1beta; Interleukin-8; Male; Meningitis, Bacterial; Meningitis, Viral; Middle Aged; Nitric Oxide; Young Adult

To study the clinical and laboratory significance of D‐lactate in the diagnosis of bacterial meningitis (BM).. The levels of D‐lactate, L‐lactate, IL-6, IL-8, and other biochemical markers were determined in 83 CSF samples from different types of meningitis and the controls.. The CSF values of D‐lactate, L‐lactate, IL-6, IL-8, erythrocytes, leukocytes, and protein were higher in patients with BM than those in the controls and patients with viral meningitis. The levels of D‐lactate, L‐lactate, IL-6, and erythrocytes in the BM group were higher than those in the tuberculous meningitis group. At the cutoff 12.8 μmol/l, D‐lactate showed the diagnostic sensitivity of 94.7%. D‐lactate gave the area under the curve (AUC) 0.905, which was higher than those of other markers. Using multiple marker detection, the AUC reached 0.956, which was the highest among all the parameters. Pearson correlation analysis revealed that D‐lactate was positively correlated to IL-6 and L‐lactate (r=0.727, 0.789 and P=0.000, 0.000, respectively).. THE CSF concentrations of D‐lactate are significantly increased in the presence of BM. Measurement of D‐lactate provides a rapid diagnosis and differential diagnosis for BM. Combination of D‐lactate with other biochemical markers improves the specificity.

Topics: Adolescent; Adult; Aged; Area Under Curve; Biomarkers; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Interleukin-6; Interleukin-8; Lactic Acid; Male; Meningitis, Bacterial; Meningitis, Viral; Middle Aged; Sensitivity and Specificity; Stereoisomerism; Tuberculosis, Meningeal

In healthy adults, the major peripheral blood γδ T-cell subset expresses the Vγ9Vδ2 TCR and displays pleiotropic features. Here we report that coculture of naive Vγ9Vδ2 T cells with phosphoantigens and a cocktail of cytokines (IL-1-β, TGF-β, IL-6, and IL-23), leads to selective expression of the transcription factor RORγt and polarization toward IL-17 production. IL-17(+) Vγ9Vδ2 T cells express the chemokine receptor CCR6 and produce IL-17 but neither IL-22 nor IFN-γ; they have a predominant terminally differentiated (CD27(-)CD45RA(+)) phenotype and express granzyme B, TRAIL, FasL, and CD161. On antigen activation, IL-17(+) Vγ9Vδ2 T cells rapidly induce CXCL8-mediated migration and phagocytosis of neutrophils and IL-17-dependent production of β-defensin by epithelial cells, indicating that they may be involved in host immune responses against infectious microorganisms. Accordingly, an increased percentage of IL-17(+) Vγ9Vδ2 lymphocytes is detected in the peripheral blood and at the site of disease in children with bacterial meningitis, and this pattern was reversed after successful antibacterial therapy. Most notably, the phenotype of IL-17(+) Vγ9Vδ2 T cells in children with meningitis matches that of in vitro differentiated IL-17(+) Vγ9Vδ2 T cells. Our findings delineate a previously unknown subset of human IL-17(+) Vγ9Vδ2 T lymphocytes implicated in the pathophysiology of inflammatory responses during bacterial infections.

Topics: Adolescent; Adult; Antigens, Bacterial; beta-Defensins; Cell Differentiation; Cell Lineage; Cells, Cultured; Child; Child, Preschool; Coculture Techniques; Female; Humans; Immunophenotyping; Interleukin-17; Interleukin-8; Male; Meningitis, Bacterial; Neutrophils; Phagocytosis; Receptors, Antigen, T-Cell, gamma-delta; Th17 Cells

Group B Streptococcus (GBS) is the leading cause of meningitis in newborn infants. Bacterial cell surface appendages, known as pili, have been recently described in streptococcal pathogens, including GBS. The pilus tip adhesin, PilA, contributes to GBS adherence to blood-brain barrier (BBB) endothelium; however, the host receptor and the contribution of PilA in central nervous system (CNS) disease pathogenesis are unknown. Here we show that PilA binds collagen, which promotes GBS interaction with the α₂β₁ integrin resulting in activation of host chemokine expression and neutrophil recruitment during infection. Mice infected with the PilA-deficient mutant exhibit delayed mortality, a decrease in neutrophil infiltration and bacterial CNS dissemination. We find that PilA-mediated virulence is dependent on neutrophil influx as neutrophil depletion results in a decrease in BBB permeability and GBS-BBB penetration. Our results suggest that the bacterial pilus, specifically the PilA adhesin, has a dual role in immune activation and bacterial entry into the CNS.

Topics: Animals; Bacterial Adhesion; Blood-Brain Barrier; Chemokines; Chemotaxis, Leukocyte; Fimbriae, Bacterial; Focal Adhesion Protein-Tyrosine Kinases; Integrin alpha2beta1; Interleukin-8; Meningitis, Bacterial; Mice; Neutrophils; Signal Transduction; Streptococcus agalactiae

Adjunctive treatment to improve outcome from bacterial meningitis has centered on dexamethasone. Among Vietnamese patients with bacterial meningitis, cerebrospinal fluid (CSF) opening pressure and CSF:plasma glucose ratios were significantly improved and levels of CSF cytokines interleukin (IL)-6, IL-8, and IL-10 and were all statistically significantly lower after treatment in patients who were randomized to dexamethasone, compared with levels in patients who received placebo.

Topics: Adolescent; Adult; Anti-Inflammatory Agents; Asian People; Child; Dexamethasone; Female; Humans; Interleukin-10; Interleukin-6; Interleukin-8; Male; Meningitis, Bacterial; Middle Aged; Vietnam; Young Adult

The aim of this study was to test the hypothesis that elevated lipopolysaccharide binding protein (LBP) serum concentration is a useful marker in the early diagnosis of invasive bacterial infection in children. We measured LBP in serum and cerebrospinal fluid (CSF) of children with proven invasive infection caused by Haemophilus influenzae, Streptococcus pneumoniae and Neisseria meningitidis.. Samples were collected from 39 children (aged 2 months to 17 years) with bacterial sepsis (n = 19) or meningitis (n = 20). Bacterial infection was diagnosed when a blood or CSF culture was positive and clinical signs of invasive infection were present. The control group consisted of serum (n = 60) and CSF (n = 19) samples from children with neurologic disease, juvenile idiopathic arthritis or viral infection. In 10 patients with bacterial infection, follow-up samples (24 and 48 hours) were available. LBP values were measured by an immunochemiluminescence analyzer (IMMULITE; DPC Biermann, Bad Nauheim, Germany) and compared with tumor necrosis factor-alpha and interleukin-8 concentrations.. The median LBP serum concentrations in patients with bacterial infection were markedly elevated compared with the control groups (45.0 [33.1-55.2] versus 8.3 [6.8-10.1] microg/mL [median and 5-95% confidence interval]; P < 0.0001). Follow-up serum values of LBP were persistently elevated despite adequate antibiotic treatment, whereas tumor necrosis factor-alpha and interleukin-8 concentrations decreased. In contrast, LBP concentrations in the CSF were below the detection limit of 0.5 microg/mL in 67% of patients with bacterial meningitis (median <0.5 microg/mL), whereas tumor necrosis factor-alpha and interleukin-8 levels were highly elevated.. LBP serum concentration is elevated in serum of children with invasive bacterial infection and could be a promising diagnostic marker.

Topics: Acute-Phase Proteins; Adolescent; Biomarkers; Carrier Proteins; Cerebrospinal Fluid; Child; Child, Preschool; Haemophilus Infections; Haemophilus influenzae; Humans; Immunoassay; Infant; Interleukin-8; Luminescent Measurements; Membrane Glycoproteins; Meningitis, Bacterial; Meningococcal Infections; Neisseria meningitidis; Pneumococcal Infections; Sepsis; Serum; Streptococcus pneumoniae; Time Factors; Tumor Necrosis Factor-alpha

Toll-like receptors (TLRs) are pattern recognition receptors (PRR) that recognize molecular structures on pathogens and activate host defenses. Although much is known about specific bacterial components that activate TLRs, few studies have addressed the question of which TLRs are involved in immune activation by live bacteria. Here, we demonstrate that live Streptococcus pneumoniae, Haemophilus influenzae type b, and Neisseria meningitidis, the three principal causes of bacterial meningitis, use distinct sets of TLRs to trigger the inflammatory response. Using human embryonic kidney 293 cell lines, each overexpressing one type of TLR, we found that S. pneumoniae triggered activation of the transcription factor nuclear factor-kappaB and expression of interleukin-8, only in cells expressing TLR2 or -9. The same response was evoked by H. influenzae in cells expressing TLR2 or -4 and by N. meningitidis in cells expressing TLR2, -4, or -9. It is interesting that the ability of S. pneumoniae and N. meningitidis to activate TLR9 was severely attenuated when bacteria had been heat-inactivated prior to stimulation of the cells. In human peripheral blood mononuclear cells, we blocked TLR2, -4, or -9 and confirmed the essential role of these TLRs and also identified differential functions of TLRs in activation of the inflammatory response. Collectively, we here demonstrate that S. pneumoniae, H. influenzae, and N. meningitidis each activate several TLRs in species-specific patterns and show that infection with live pathogens may lead to activation of PRR not targeted by inactivated bacteria.

Topics: Cell Line; Cells, Cultured; DNA, Bacterial; Haemophilus influenzae type b; Humans; Immunity, Innate; Interleukin-8; Meningitis, Bacterial; Neisseria meningitidis; NF-kappa B; Signal Transduction; Species Specificity; Streptococcus pneumoniae; Toll-Like Receptor 2; Toll-Like Receptor 4; Toll-Like Receptor 9; Transfection

The interactions of bacterial pathogens with cells of the human leptomeninges are critical events in the progression of meningitis. An in vitro model based on the culture of human meningioma cells was used to investigate the interactions of the meningeal pathogens Escherichia coli K1, Haemophilus influenzae, Neisseria meningitidis and Streptococcus pneumoniae. A rank order of association with meningioma cells was observed, with N. meningitidis showing the highest levels of adherence, followed by E. coli, S. pneumoniae and H. influenzae. Neisseria meningitidis and H. influenzae did not invade meningioma cells or induce cell death, but induced a concentration-dependent secretion of inflammatory mediators. Neisseria meningitidis induced higher levels of IL-6, MCP-1, RANTES and GM-CSF than H. influenzae, but there was no significant difference in the levels of IL-8 induced by both pathogens. Streptococcus pneumoniae was also unable to invade meningioma cells, but low concentrations of bacteria failed to stimulate cytokine secretion. However, higher concentrations of pneumococci led to cell death. By contrast, only E. coli K1 invaded meningioma cells directly and induced rapid cell death before an inflammatory response could be induced. These data demonstrate that the interactions of different bacterial pathogens with human meningeal cells are distinct, and suggest that different intervention strategies may be needed in order to prevent the morbidity and mortality associated with bacterial meningitis.

Topics: Bacterial Adhesion; Cell Death; Cell Line, Tumor; Chemokine CCL2; Chemokine CCL5; Colony Count, Microbial; Cytokines; Cytoplasm; Escherichia coli; Granulocyte-Macrophage Colony-Stimulating Factor; Haemophilus influenzae; Humans; Interleukin-6; Interleukin-8; Meninges; Meningioma; Meningitis, Bacterial; Microscopy, Confocal; Microscopy, Electron; Neisseria meningitidis; Streptococcus pneumoniae

Bacterial meningitis is still associated with high mortality rate and severe neurological sequels. The aim of the study was to assess correlation between concentration of proinflammatory cytokines (TNF-alpha, IL-1 beta, IL-8) in the cerebrospinal fluid (CSF) and patient condition described on the basis of Glasgow Coma Scale (GCS), changes in the CSF (pleocytosis, protein and glucose level), mortality rate and occurrence of neurological complications. 42 patients with bacterial meningitis have been analysed. Control group consisted of 25 patients with viral meningitis and 23 patients without meningitis. In analysed group with bacterial meningitis the correlation between number of scores aggregated by patients in GCS and outcome has been observed. Concentration of TNF-alpha, IL-1 beta, IL-8 in CSF of patient with bacterial meningitis was significantly higher (mean value; 705.2 pg/ml, 401.1 pg/ml and 1696.0 pg/ml) than in control group (viral meningitis: 7.93 pg/ml, 31.89 pg/ml, 405.28 pg/ml, without meningitis: 0.38 pg/ml, 2.55 pg/ml, 32.56 pg/ml). Negative correlation between concentration of investigated cytokines in the CSF of patient with bacterial meningitis and GCS has been observed. Furthermore TNF-alpha and IL-8 levels correlated with pleocytosis, and protein and glucose levels, whereas IL-1 beta correlated with pleocytosis and protein level in CSF. Connection between TNF-alpha and IL-1 beta but not IL-8 level and outcome of bacterial meningitis has been observed. High TNF-alpha in the CSF (median value 953 pg/ml) was associated with significant risk of patient death. IL-1 beta has been better prognostic indicator. Patients who developed neurological sequels had median value of IL-1 beta level 401.3 pg/ml, and those who died had 585.9 pg/ml vs 244.7 pg/ml in the group who survived without any complications. Analysis of the ROC curve-revealed, that concentration of IL-1 beta > or = 289.9 pg/ml with 88.9% sensitivity and 67.7% specifity differentiate cases who at risk for death. For TNF-alpha the cut-off was > or = 538.9 pg/ml. The sensitivity for determined critical point was 77%, and specificity was 68.7%. Our investigation confirm that TNF alpha, IL-1 beta, IL-8 are useful in differential diagnosis of neuroinfections. Assessment of patients with bacterial meningitis on the basis of GCS is helpful to establish prognosis, and CGS seems to correlate with the intensity of inflammation in the CSF. High concentration of TNF-alpha, and IL-1 beta in the CS

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Female; Glasgow Coma Scale; Humans; Interleukin-1; Interleukin-8; Male; Meningitis, Bacterial; Meningitis, Viral; Middle Aged; Prognosis; Sensitivity and Specificity; Survival Analysis; Tumor Necrosis Factor-alpha

To determine the level of serum procalcitonin and cerebrospinal fluid cytokines in children with bacterial or viral meningitis and to document the use of these parameters in differential diagnosis.. Before the start of antibiotic treatment, serum procalcitonin and tumor necrosis factor alpha levels were found to be higher in acute bacterial meningitis compared with viral meningitis and with the control group. Similarly, cerebrospinal fluid interleukin-6 levels were found to be significantly higher in children with acute bacterial meningitis compared with viral meningitis. However, no significant difference was determined between groups in respect to the cerebrospinal fluid interleukin-8 level.. Serum procalcitonin and cerebrospinal fluid tumor necrosis factor alpha levels can be used in the early diagnosis of bacterial meningitis. Similarly, they may be useful adjuncts in differential diagnosis of bacterial and viral meningitis.

Topics: Calcitonin; Calcitonin Gene-Related Peptide; Child; Child, Preschool; Cytokines; Diagnosis, Differential; Early Diagnosis; Female; Humans; Infant; Interleukin-6; Interleukin-8; Male; Meningitis, Bacterial; Meningitis, Viral; Protein Precursors; Tumor Necrosis Factor-alpha

The combined expression of the inflammatory mediators, matrix metalloproteinases (MMPs), soluble form of intracellular adhesion molecule ICAM-1 (sICAM-1) and interleukin (IL)-8, was evaluated in children infected with bacterial or viral meningitis. MMP-2 and IL-8 were detected in all CSF samples and were enhanced in both bacterial and viral infected samples, compared to those from control children. The expression of MMP-9 as well as sICAM-1 was not detected in control CSF while observed in viral infected and further elevated in bacterial infected samples. This pilot study supports a role for MMPs, IL-8 and sICAM in infectious meningitis and suggests further research to determine their possible use as biomarkers for various forms of meningeal infection as well as the use of their specific antagonists as potential therapeutic agents for central nervous system (CNS) inflammatory processes.

Topics: Biomarkers; Child; Gelatinases; Humans; Inflammation; Intercellular Adhesion Molecule-1; Interleukin-8; Matrix Metalloproteinase 2; Matrix Metalloproteinase 8; Matrix Metalloproteinase 9; Matrix Metalloproteinases; Meningitis, Bacterial; Meningitis, Viral; Reference Values

Combination therapy that includes fusidic acid, an antimicrobial agent highly active against staphylococci, has been recommended in the treatment of patients with Staphylococcus aureus meningitis. The aim of this study was to evaluate the pharmacokinetic, CSF bactericidal and anti-inflammatory properties of fusidic acid.. The pharmacokinetics, treatment efficacy and parameters of the meningeal inflammatory response were studied in rabbits, using an experimental meningitis model against S. aureus (MICs of fusidic acid and methicillin were 0.125 and 1 mg/L, respectively).. Fusidic acid entered the CSF, with peak values within 0.5-1 h of the intravenous bolus injection/infusion and with a percentage penetration (AUCCSF/AUCserum) into uninfected and purulent CSF of 1.9% +/- 0.7 and 4.5% +/- 0.7, respectively. Rabbits treated with antibiotics [fusidic acid 80 mg/kg/6 h (n = 6), methicillin 80 mg/kg/3 h (n = 7) and the two combined (n = 6)] had significantly higher bacterial kill rates than untreated controls (n = 6, P < 0.05). Combination therapy was less effective, with significantly less killing after 6 h of treatment than methicillin alone (P < 0.05). CSF white blood cells and CSF levels of interleukin-8 (IL-8), glucose, lactate and protein were altered during staphylococcal meningitis, but with no significant difference between antibiotic-treated and untreated rabbits.. Antagonism between methicillin and fusidic acid was observed in staphylococcal meningitis.

Topics: Animals; Anti-Bacterial Agents; Drug Therapy, Combination; Fusidic Acid; Glucose; Interleukin-8; Leukocyte Count; Meningitis, Bacterial; Methicillin; Microbial Sensitivity Tests; Penicillins; Rabbits; Staphylococcal Infections; Staphylococcus aureus

Meningitis occurs when blood-borne pathogens cross the blood-brain barrier (BBB) in a complex interplay between endothelial cells and microbial gene products. We sought to understand the initial response of the BBB to the human meningeal pathogen group B Streptococcus (GBS) and the organism's major virulence factors, the exopolysaccharide capsule and the beta-hemolysin/cytolysin toxin (beta-h/c). Using oligonucleotide microarrays, we found that GBS infection of human brain microvascular endothelial cells (HBMEC) induced a highly specific and coordinate set of genes including IL-8, Groalpha, Grobeta, IL-6, GM-CSF, myeloid cell leukemia sequence-1 (Mcl-1), and ICAM-1, which act to orchestrate neutrophil recruitment, activation, and enhanced survival. Most strikingly, infection with a GBS strain lacking beta-h/c resulted in a marked reduction in expression of genes involved in the immune response, while the unencapsulated strain generally induced similar or greater expression levels for the same subset of genes. Cell-free bacterial supernatants containing beta-h/c activity induced IL-8 release, identifying this toxin as a principal provocative factor for BBB activation. These findings were further substantiated in vitro and in vivo. Neutrophil migration across polar HBMEC monolayers was stimulated by GBS and its beta-h/c through a process involving IL-8 and ICAM-1. In a murine model of hematogenous meningitis, mice infected with beta-h/c mutants exhibited lower mortality and decreased brain bacterial counts compared with mice infected with the corresponding WT GBS strains.

Topics: Bacterial Proteins; Blood-Brain Barrier; Brain; Cell Movement; Disease Models, Animal; Endothelium, Vascular; Enzyme-Linked Immunosorbent Assay; Gene Expression Profiling; Hemolysin Proteins; Humans; Interleukin-8; Meningitis, Bacterial; Neutrophils; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; Streptococcus agalactiae

CXCL5 (epithelial-cell-derived neutrophil-activating protein (ENA-)78) is a CXC-chemokine that specifically acts on neutrophils. To obtain insight into the extent of local presence and action of CXCL5 during bacterial meningitis, we measured its concentrations in cerebrospinal fluid (CSF) of patients with culture-proven bacterial meningitis (n=14), aseptic meningitis (n=6), and controls (n=32) and compared these results with levels of other CXC-chemokines, CXCL8- (interleukin-8) and CXCL1-related oncogene (growth-related oncogene (GRO)-alpha). Patients with bacterial meningitis had profoundly elevated CSF concentrations of all three chemokines. CXCL5 was not detectable in patients with aseptic meningitis or control subjects. CSF from patients with bacterial meningitis exerted chemotactic activity towards neutrophils, which was partially inhibited by neutralizing antibodies against CXCL5 and CXCL8, but not CXCL1. CSF from controls exerted minor chemotactic activity, which could be strongly enhanced by the addition of recombinant CXCL5, CXCL8 or CXCL1. During bacterial meningitis, CXCL5 is elevated in CSF, where it is involved in the recruitment of neutrophils to the central nervous system.

Topics: Adolescent; Chemokine CXCL1; Chemokine CXCL5; Chemokines, CXC; Chemotaxis, Leukocyte; Child; Humans; Intercellular Signaling Peptides and Proteins; Interleukin-8; Klebsiella Infections; Meningitis, Aseptic; Meningitis, Bacterial; Meningitis, Meningococcal; Meningitis, Pneumococcal; Neutrophil Activation

lnterleukin-8 (IL-8) is produced in monocytes and vascular endothelial cells in response to stimulation with bacteria or lipopolysaccharides, and is released from these cells into blood stream or tissue fluid.. Cerebrospinal fluid (CSF) levels of interleukin-8 in 56 children with nonbacterial, bacterial and tuberculous meningitis (TBM), and in 15 control subjects were analyzed to evaluate the involvement of this cytokine in the pathogenesis acute bacterial meningitis and their discriminative value between different etiologies of meningitis. The kinetics of IL-8 concentrations during the course of bacterial meningitis was also evaluated in patients. IL-8 levels were significantly higher in bacterial and TBM than in aseptic meningitis and in control subjects (p < 0.0001).. There was no difference in the levels of IL-8 between the non-bacterial meningitis and control groups. The analysis of the kinetics of production of IL-8 in patients with bacterial meningitis showed that the SSF concentrations of this cytokine decreased to undetectable values in recovery stage. Conversely in patients with TBM the concentrations of IL-8 were elevated in two weeks after beginning the specific treatment.. The results suggest that determining IL-8 levels may be useful in the differential diagnosis.

Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Infant, Newborn; Interleukin-8; Meningitis, Aseptic; Meningitis, Bacterial; Tuberculosis, Meningeal

To evaluate whether cerebrospinal fluid concentrations of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta, IL-6, or IL-8 may be used as diagnostic markers for the differential diagnosis of aseptic vs. bacterial meningitis and/or ventriculitis in neurosurgical patients.. Prospective, observational study.. University teaching hospital.. A total of 112 cerebrospinal fluid samples from 14 asymptomatic patients with normal cerebrospinal fluid after neurosurgery, 27 asymptomatic and 19 symptomatic patients with postneurosurgical aseptic meningitis, 32 patients with postneurosurgical cerebrospinal fluid infection, and 20 with severe subarachnoid and/or cerebral hemorrhage.. Specific ELISA kits were used to analyze TNF-alpha, IL-1beta, IL-6, and IL-8 concentrations on cerebrospinal fluid samples. Elevations in cerebrospinal fluid concentrations of TNF-alpha, IL-1beta, IL-6, and IL-8 were induced by different diseases or neurosurgical procedures, but cerebrospinal fluid bacterial infection induced the highest concentrations. To discriminate between aseptic cerebrospinal fluid pleocytosis and cerebrospinal fluid infection with a specificity of 95%, cerebrospinal fluid leukocyte count >1700/mL, TNF-alpha >150 pg/mL, and IL-1beta >90 pg/mL showed sensitivities of 51%, 74%, and 90%, respectively. Sufficiently sensitive and specific cutoff points could not be found for cerebrospinal fluid IL-6 or IL-8.. Cerebrospinal fluid IL-1beta appears to be the best biochemical marker of cerebrospinal fluid infection in neurosurgical patients.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Biomarkers; Case-Control Studies; Cerebral Hemorrhage; Child; Child, Preschool; Cytokines; Diagnosis, Differential; Encephalitis; Female; Humans; Interleukin-1; Interleukin-6; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Neurosurgical Procedures; Postoperative Complications; Prospective Studies; Tumor Necrosis Factor-alpha

Cerebrospinal fluid (CSF) of patients with purulent meningitis contains a high concentration of interleukin (IL)-8. Recently, the presence of anti-IL-8 auto-antibodies was noted in blood and alveolar fluid. Therefore, measurement of the concentration of anti-IL-8 auto-antibodies was attempted in CSF of children with and without meningitis.. We measured the concentration of anti-IL-8 auto-antibodies in CSF of children with purulent or aseptic meningitis and those without meningitis. The CSF obtained on admission showed a significantly higher concentration of anti-IL-8 IgG and IgM auto-antibodies in children with purulent meningitis, compared with those with aseptic meningitis or without meningitis. Among the three groups of children, the concentration of IL-8 was also significantly higher in CSF of children with purulent meningitis.. Because the anti-IL-8 IgG auto-antibody binds to IL-8 and inhibits IL-8 interaction with specific receptors on neutrophils, the presence of anti-IL-8 auto-antibodies seems to provide a mechanism that limits the bioavailability of free IL-8 in CSF.

Topics: Autoantibodies; Child, Preschool; Humans; Infant; Infant, Newborn; Interleukin-8; Meningitis, Aseptic; Meningitis, Bacterial; Reference Values; Suppuration

To determine interleukin (IL)-8 concentrations in ventricular cerebrospinal fluid from children with severe traumatic brain injury (TBI).. Prospective study.. University children's hospital.. Twenty-seven children hospitalized with severe TBI (Glasgow Coma Scale score < or =8), seven children with cerebrospinal fluid culture-positive bacterial meningitis, and twenty-four age-equivalent controls.. Placement of an intraventricular catheter and continuous drainage of cerebrospinal fluid.. Median [range] cerebrospinal fluid IL-8 concentration in children with TBI (0-12 hrs) (4,452.5 [0-20,000] pg/mL) was markedly greater than that in controls (14.5 [0-250]) (p < .0001) and equivalent to concentrations in children with meningitis (5,300 [1,510-22,000] pg/mL) (p = .33). Cerebrospinal fluid IL-8 remained increased in children with severe TBI for up to 108 hrs after injury. Univariate logistic regression analysis demonstrated an association between cerebrospinal fluid IL-8 and child abuse (p = .07) and mortality (p = .01). Multivariate analysis demonstrated a strong, independent association between cerebrospinal fluid IL-8 and mortality (p = .01).. The data are consistent with an acute inflammatory component of TBI in children and suggest an association between cerebrospinal fluid IL-8 and outcome after TBI. IL-8 may represent a potential target for anti-inflammatory therapy.

Topics: Acute Disease; Adolescent; Biomarkers; Child; Child, Preschool; Craniocerebral Trauma; Enzyme-Linked Immunosorbent Assay; Female; Humans; Infant; Interleukin-8; Logistic Models; Male; Meningitis, Bacterial; Prospective Studies; Time Factors

Interleukin-8 (IL-8) is elevated in the cerebrospinal fluid (CSF) of patients with meningitis and is proposed to participate in subarachnoid-space pleocytosis. However, intracisternal injection of IL-8 into rabbits failed to induce indices typical of meningitis (leukocyte, tumor necrosis factor, or protein accumulation in the CSF or histopathological changes), indicating that merely increasing the CSF level of this chemokine is insufficient to induce inflammation in this anatomical site. IL-8 treatment did not affect inflammatory responses to subsequently intracisternally administered lipopolysaccharide (LPS). IL-8 was chemotactic for rabbit neutrophils in vitro, and subcutaneous injection of IL-8 (diluted in buffer or CSF) proved the in vivo activity of this peptide and suggested the absence of an IL-8 inhibitor in normal rabbit CSF. LPS-dependent pleocytosis was only slightly diminished by intracisternally administered murine anti-rabbit IL-8 monoclonal antibody (MAb) WS-4 but was dramatically reduced by intravenously administered MAb. Therefore, elevated CSF IL-8 levels may contribute to, but cannot solely account for, neutrophil influx into the subarachnoid space during meningitis. However, inhibition of IL-8 activity of the bloodstream side of the blood-brain barrier effectively reduces pleocytosis, indicating a central role of IL-8 in neutrophil influx into CSF during bacterial meningitis. Thus, inhibition of IL-8 is a possible therapeutic target for adjunct treatment of meningitis.

Topics: Animals; Antibodies, Monoclonal; Chemotaxis, Leukocyte; Humans; Interleukin-8; Leukocytosis; Lipopolysaccharides; Meningitis, Bacterial; Neutralization Tests; Neutrophils; Rabbits

We serially measured concentrations of interleukin (IL)-8 and anti-IL-8 IgG autoantibody in cerebrospinal fluid of infants with bacterial meningitis, and also measured these concentrations in cerebrospinal fluid obtained from infants without meningitis on admission. We have reported that the IL-8 concentration in cerebrospinal fluid of infants with purulent meningitis rapidly decreases after the initiation of therapy. Thus, in the present study, the IL-8 concentration in infants with purulent meningitis only before the initiation of therapy was significantly higher compared with that in infants without meningitis. However, the concentration of anti-IL-8 IgG autoantibody was still high after the initiation of therapy. The concentration of anti-IL-8 IgG autoantibody was significantly higher compared with that in infants without meningitis until the 15th day after the initiation of therapy. The time lag between the decrease of IL-8 and anti-IL-8 IgG autoantibody demonstrated in the present study could be used to indicate the past presence of a large amount of IL-8, even if the IL-8 concentration was already low.

Topics: Autoantibodies; Child; Child, Preschool; Humans; Immunoglobulin G; Infant; Interleukin-8; Meningitis, Bacterial

Steroid responsive meningitis-arteriitis (SRMA) is a systemic immune disorder, characterized by inflammatory-stenosing lesions of the meningeal arteries and meningitis. The predilection of the disease for the central nervous system (CNS) remains unexplained. In this study, chemotactic activity and chemotactic factors were measured in the cerebrospinal fluid (CSF) of dogs with SRMA. CSF of dogs with SRMA exerted a marked chemotactic activity for leukocytes. Neutrophils were attracted to a similar degree as by CSF from animals with bacterial encephalitis. Chemotactic activity was also noted for mononuclear cells, however, by far weaker than in CSF from animals with viral encephalitis. While the inflammatory process could be suppressed with glucocorticoid treatment, the chemotactic activity of CSF persisted. We could identify IL-8-like activities using a desensitization assay in the CSF of animals with SRMA and also found increased IgA levels. Increased chemotactic activity for polymorphonuclear leukocytes correlated positively with the levels of IL-8-like activity in CSF. Our observations clearly suggest that in SRMA chemotactic factors are generated in the CNS. These include IL-8, but probably also others. The intensity of this production appears to correlate with IgA levels in the CSF suggesting either a causal link or reflecting the severity of the inflammation.

Topics: Animals; Arteritis; Cerebral Arteries; Cerebrospinal Fluid; Chemotaxis; Distemper; Dogs; Glucocorticoids; Immunoglobulin A; Interleukin-8; Leukocyte Count; Lymphocytes; Meningitis, Bacterial; Neutrophils

The concentrations of the chemokines IL-8, monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1alpha (MIP-1alpha) were measured in 120 CSF samples from 23 patients with pyogenic meningitis and from 11 patients with tuberculous meningitis (TBM) and in 10 CSF from subjects with non-infectious neurological diseases. The chemokine concentrations in patients with meningitis were significantly higher than in control subjects (P<0.0001). The highest CSF levels were found for IL-8 (median 2917 pg/ml) and MCP-1 (median 2557 pg/ml), whereas those of MIP-1alpha were less significantly elevated (median 24 pg/ml) (P<0.0001). Patients with pyogenic meningitis had higher levels of IL-8 and MCP-1 than those with TBM (P<0.0001). In serial samples from patients with pyogenic meningitis IL-8 levels declined before MCP-1 and MIP-alpha. In the case of TBM, IL-8, MCP-1 and MIP-1alpha decreased more gradually during treatment and were detectable in the CSF for several weeks, without any characteristic time course of elimination. These data indicate that patients with pyogenic meningitis and TBM show different chemokine profiles in CSF. The distinct chemokine pattern could be responsible for a differential attraction and activation of leucocytes in the CSF which is reflected in differences in the inflammatory response and clinical course of pyogenic meningitis and TBM.

Topics: Adult; Chemokine CCL2; Chemokine CCL3; Chemokine CCL4; Child; Child, Preschool; Humans; Infant; Interleukin-8; Macrophage Inflammatory Proteins; Meningitis, Bacterial; Middle Aged; Tuberculosis, Meningeal

To assess the role of interleukin-12 (IL-12) and gamma interferon (IFN-gamma) in children with bacterial meningitis, bioactive IL-12 (p70) and the inactive subunit p40 and IFN-gamma were measured in serum and cerebrospinal fluid (CSF) from 35 children with bacterial meningitis and 10 control subjects. The production of IFN-gamma is induced by IL-12 with tumor necrosis factor alpha (TNF-alpha) as a costimulator and inhibited by IL-10. CSF concentrations of IL-12 p40 as well as those of IFN-gamma were markedly elevated, whereas IL-12 p70 was hardly detectable. Detectable CSF levels of IFN-gamma correlated positively with IL-12 p40 (r = 0.40, P = 0.02) and TNF-alpha (r = 0.46, P = 0.04) but not with IL-6, IL-8, or IL-10. In contrast to CSF levels of TNF-alpha, IL-12, and IL-10, those of IFN-gamma were significantly higher in patients with pneumococcal meningitis than in children with meningitis caused by Haemophilus influenzae and Neisseria meningitidis, presumably because of a high CSF TNF-alpha/IL-10 ratio in the former. We suggest that IL-12- and TNF-alpha-induced IFN-gamma production may contribute to the natural immunity against microorganisms in the CSF compartment during the acute phase of bacterial meningitis.

Topics: Adolescent; Child; Child, Preschool; Humans; Infant; Interferon-gamma; Interleukin-12; Interleukin-6; Interleukin-8; Meningitis, Bacterial; Subarachnoid Space; Tumor Necrosis Factor-alpha

Meningitis is accompanied by a differential immigration of leukocytes into the subarachnoid space. Since the mechanisms regulating leukocyte invasion are still incompletely understood, we studied the release of the neutrophil-attracting alpha-chemokines IL-8 and GRO-alpha and the mononuclear cell-attracting beta-chemokines MCP-1, MIP-1alpha, and RANTES during meningitis. In 48 paired CSF and serum samples from patients hospitalized for meningitic symptoms, high levels of IL-8, GRO-alpha, and MCP-1 were detected in the CSF during bacterial and abacterial meningitis. Elevated chemokine levels were not found in the blood serum samples taken in parallel. The release of MIP-1alpha or RANTES was below detection limits. The IL-8 and GRO-alpha levels significantly correlated with the number of immigrated granulocytes in the CSF of patients with bacterial meningitis. A similar correlation was found when MCP-1 levels and the mononuclear cell count were analyzed in abacterial meningitis. These findings suggest that the local production of the alpha-chemokines IL-8 and GRO-alpha and of the beta-chemokine MCP-1 represents the major chemoattractant stimulus for the differential recruitment of leukocytes into the subarachnoid space during meningitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Chemokines; Female; Humans; Interleukin-8; Leukocyte Count; Male; Meningitis; Meningitis, Bacterial; Meningitis, Viral; Middle Aged; Retrospective Studies

Using a monoclonal antibody enzyme immunoassay, the concentration of interleukin-8 (IL-8) in cerebrospinal fluid (CSF) from 52 patients suspected of having meningitis was studied. The CSF IL-8 concentration was significantly higher in septic meningitis of known and unknown etiology than in aseptic meningitis and significantly higher in aseptic meningitis than in patients without meningitis. The CSF levels of IL-8 correlated with the levels of tumor necrosis factor-alpha, leukocyte count, neutrophil count, protein level, CSF/blood glucose ratio, and the number of days patients were hospitalized. The IL-8 values used to distinguish septic from aseptic meningitis, at a cut-off point of 3.00 micrograms/l, showed a sensitivity of 81%, a specificity of 92%, and a positive predictive value of 96%. The results suggest that determining IL-8 levels may be useful in the differential diagnosis of meningitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Bacteremia; Child; Child, Preschool; Diagnosis, Differential; Female; Humans; Infant; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Middle Aged; Predictive Value of Tests; Sensitivity and Specificity; Tumor Necrosis Factor-alpha

Interleukin (IL)-8 concentrations were analyzed in 70 cerebrospinal fluid (CSF) samples from patients with meningitis of different etiologies and in 34 normal CSF samples. Patient groups included those with pyogenic meningitis, viral meningitis, self-resolving aseptic meningitis without a specific diagnosis, and meningitis of other etiologies and normal CSF from patients with and without neurologic disease. All samples from patients with pyogenic meningitis (18) but only 3 from patients with meningitis of other etiologies and with CSF polymorphonuclear leukocyte (PMNL) counts > or = 80% had IL-8 levels > or = 2.5 ng/mL. IL-8 was above the normal level (< or = 0.5 ng/mL) in samples from 5 of 13 viral and 8 of 23 self-resolving aseptic meningitis patients and in 7 of 13 samples from patients with meningitis caused by other microorganisms. There was a significant relationship between IL-8 levels and CSF PMNL counts in patients with nonpyogenic meningitis. The data suggest a possible role of IL-8 as PMNL chemotactic factor in different infections of the subarachnoid space, not only in pyogenic meningitis.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Case-Control Studies; Child; Child, Preschool; Female; Humans; Infant; Inflammation; Interleukin-8; Leukocyte Count; Male; Meningitis; Meningitis, Aseptic; Meningitis, Bacterial; Meningitis, Fungal; Meningitis, Viral; Middle Aged; Neutrophils

Topics: Child; Child, Preschool; Female; Humans; Infant; Infant, Newborn; Interleukin-8; Male; Meningitis, Bacterial; Suppuration; Tuberculosis, Meningeal

Interleukin-8 (IL-8) elaborated by monocytes and endothelial cells is a cytokine which is responsible for adhesion of leucocytes to vascular endothelium and migration of neutrophils into the cerebrospinal fluid (CSF) from the intravascular space. The inflammation in meningitis is elicited by the cytokine release from leucocytes which encounter micro-organisms in the arachnoid or subarachnoid space. In bacterial meningitis, tumour necrosis factor (TNF), IL-1 and IL-6 are produced vigorously, and initiate and augment the inflammation in the central nervous system. In this study, utilizing a quantitative immunometric sandwich enzyme immunoassay, the concentration of IL-8 was investigated in the CSF of patients with bacterial meningitis, patients with aseptic meningitis, and patients with gastroenteritis who served as controls. The IL-8 concentration was markedly higher in the CSF of patients with bacterial meningitis (224 +/- 2.57 pg/ml; mean +/- SD) than in the CSF of patients with aseptic meningitis (less than 30 pg/ml). The IL-8 level in the CSF of patients with aseptic meningitis did not differ from that in the CSF of the patients with gastroenteritis (less than 30 pg/ml). The augmented production of IL-8 in CSF may account for the inflammation in bacterial meningitis being more severe than that in aseptic meningitis.

Topics: Acute Disease; Child; Child, Preschool; Female; Gastroenteritis; Humans; Infant; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial

Cytokines at an inflammatory site may be a better indicator of the clinical severity of an infectious disease than the serum levels of the cytokines. Concentrations of interleukin-1 beta (IL-1 beta) in paired samples of cerebrospinal fluid (CSF) from 10 rabbits with experimental bacterial meningitis caused by H. influenzae type b, were measured, and compared to the concentrations of four cytokines; IL-1 beta, interleukin-6 (IL-6), interleukin-8 (IL-8) and tumor necrosis factor-alpha (TNF-alpha) in CSF samples from 45 children with or without meningitis. The IL-1 beta concentrations in the CSF from rabbits with experimental meningitis were significantly higher than the concentrations in control animals without meningitis (p < 0.001). The mean CSF concentrations of IL-8 from meningitic children were significantly higher than in the control group without meningitis (p < 0.005). TNF-alpha was only detected in septic meningitis. Assays of IL-6, however, were not significantly different in the septic meningitis group, the aseptic meningitis group and the non-meningitis group. These data indicate a possible role of IL-1 beta, IL-8 and TNF-alpha as mediators in the meningeal inflammatory process in patients with meningitis and TNF-alpha, in particular, may play a role in the pathogenesis of septic meningitis.

Topics: Adolescent; Adult; Animals; Child; Child, Preschool; Female; Humans; Infant; Interleukin-1; Interleukin-6; Interleukin-8; Male; Meningitis, Aseptic; Meningitis, Bacterial; Rabbits; Tumor Necrosis Factor-alpha