interleukin-8 and Meningitis--Viral

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

Neurological manifestations of Behçet's disease (neuro-Behçet's disease) present in 5-30% of patients. Although cytokines play a pivotal role in pathogenesis of Behçet's disease, published studies about the cerebrospinal fluid (CSF) levels of cytokines in neuro-Behçet's disease are scanty.. Nine patients with active parenchymal, one patient with non-parenchymal neuro-Behçet's disease, six patients with headache attributed to Behçet's disease, 13 patients with viral meningitis, and 19 healthy controls were recruited. Interleukin 6, 8, 10, tumor necrotic factor-alpha, and interferon-gamma were measured in the CSF using enzyme-linked immunosorbent assay method.. Patients with viral meningitis had significantly higher levels of all investigated cytokines except for interferon-gamma in comparison with the patients with parenchymal neuro-Behçet's disease, headache attributed to Behçet's disease and controls (P values <0.05). CSF interleukin 6 was significantly higher in patients with parenchymal neuro-Behçet's disease in comparison with the controls (P=0.025). CSF levels of investigated cytokines had no significant difference between patients with headache attributed to Behçet's disease and controls (P values >0.05). Patients with headache attributed to BD and patients with parenchymal NBD had no significant difference in measured cytokines (P values >0.05).. In contrast to some previous studies, our investigation showed loss of analogy between CSF cytokine profiles of patients with parenchymal neuro-Behçet's disease and viral meningitis. Also we postulated a crucial role for interleukin 6 in immunopathogenesis of neuro-Behçet's disease.

Topics: Adult; Behcet Syndrome; Case-Control Studies; Central Nervous System Diseases; Cytokines; Female; Headache; Humans; Interferon-gamma; Interleukin-10; Interleukin-6; Interleukin-8; Male; Meningitis, Viral; Reference Values; Statistics, Nonparametric; Tumor Necrosis Factor-alpha; Young Adult

Aicardi-Goutières syndrome (AGS) presents as a severe autosomal recessively inherited neurological brain disease. Clinical and neurological manifestations closely resemble those of congenital viral infection and are generally attributed to a perturbation of innate immunity including a long lasting lymphocytosis and production of interferon-alpha (IFNalpha) in the central nervous system. To clarify the innate immune response evoked in these diseases, we used a 30-mer multiplexed luminex system to measure multiple cytokines and growth factors in the cerebrospinal fluid and serum of patients with AGS and viral meningitis or encephalitis, and febrile controls in whom infection could not be substantiated. In addition to the previously described IFNalpha, both AGS and viral diseases were characterized by expression of CXCL10 and CCL2. In contrast to AGS, viral infection resulted in high levels of IL-6 and CXCL8 in the CNS. Postmortem immunohistochemical staining of brain sections showed that in both AGS and viral CNS infection, astrocytes were responsible for the production of cytokines and not the infiltrating leukocytes. In summary, our data indicate that astrocytes are the predominant cell type responsible for the production of IFNalpha and CXCL10 in AGS. Whereas IFNalpha is assumed to be involved in the neurodegeneration, calcifications and seizures in AGS, CXCL10 may act as the chemoattractant responsible for the influx of activated lymphocytes into the brain. The lack of the inflammatory cytokines IL-6 and CXCL8 in AGS suggest that the neuroinflammatory reaction in this disease is distinct from viral disease.

Topics: Abnormalities, Multiple; Adult; Aged; Astrocytes; Brain Diseases; Calcinosis; Chemokine CXCL10; Child; Child, Preschool; Encephalitis; Female; Gliosis; Humans; Infant; Infant, Newborn; Interferon-alpha; Interleukin-6; Interleukin-8; Male; Meningitis, Viral; Middle Aged; Postmortem Changes

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

High doses of adenotk were injected into the cerebrospinal fluid of rats and nonhuman primates (Macaca mulatta). Vector administration was followed by ganciclovir administration for 14 days. Despite the absence of clinical symptoms, analysis of the cerebrospinal fluid (CSF) and histopathological examination of the central nervous system (CNS) of the monkeys (3 weeks after vector injection) were consistent with a viral meningitis. Immunohistochemical analysis of the inflammatory infiltrates in the monkeys revealed the presence of T and B lymphocytes, indicating a combined cellular and humoral immune response to the vector. This latter was supported by the finding of intrathecal anti-adenovirus antibody synthesis. Rats receiving high intrathecal adenotk doses showed a transient and dose-dependent clinical toxicity consisting of lethargy, hyperemic eyes and weight loss. Histopathological examination of the meninges showed a shift from polymorphonuclear infiltrates during the first post-injection days to clusters of mononuclear cells after 7 days. Acute toxicity is probably related to the early, innate immune response to the vector. In a separate experiment, high levels of IL-8 and IL-6, were measured during the first 2-3 post-injection days in the CSF of two monkeys which received intrathecal adenoLacZ. Therefore, these cytokines seem to play an important role in initiating the nonspecific immune response. In one monkey which received adenotk, recombinant adenovirus was cultured from serum samples obtained at the 7th post-injection day. At this time-point, no vector could be isolated from CSF samples. Based on these preclinical data, we recommend careful dose finding for clinical studies that aim to treat patients with leptomeningeal metastases.

Topics: Adenoviridae; Adenoviridae Infections; Animals; Antiviral Agents; Arachnoid Cysts; Brain; Cerebrospinal Fluid; Female; Ganciclovir; Genetic Therapy; Genetic Vectors; Immunohistochemistry; Interleukin-6; Interleukin-8; Macaca mulatta; Male; Meningitis, Viral; Rats; Rats, Inbred F344; Simplexvirus; Spinal Cord; Thymidine Kinase

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

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