interleukin-8 and Meningitis--Pneumococcal

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

Streptococcus pneumoniae (SPN), the leading cause of meningitis in children and adults worldwide, is associated with an overwhelming host inflammatory response and subsequent brain injury. Here we examine the global response of the blood-brain barrier to SPN infection and the role of neuraminidase A (NanA), an SPN surface anchored protein recently described to promote central nervous system tropism. Microarray analysis of human brain microvascular endothelial cells (hBMEC) during infection with SPN or an isogenic NanA-deficient (ΔnanA) mutant revealed differentially activated genes, including neutrophil chemoattractants IL-8, CXCL-1, CXCL-2. Studies using bacterial mutants, purified recombinant NanA proteins and in vivo neutrophil chemotaxis assays indicated that pneumococcal NanA is necessary and sufficient to activate host chemokine expression and neutrophil recruitment during infection. Chemokine induction was mapped to the NanA N-terminal lectin-binding domain with a limited contribution of the sialidase catalytic activity, and was not dependent on the invasive capability of the organism. Furthermore, pretreatment of hBMEC with recombinant NanA protein significantly increased bacterial invasion, suggesting that NanA-mediated activation of hBMEC is a prerequisite for efficient SPN invasion. These findings were corroborated in an acute murine infection model where we observed less inflammatory infiltrate and decreased chemokine expression following infection with the ΔnanA mutant.

Topics: Animals; Blood-Brain Barrier; Brain; Chemokine CCL20; Chemokine CXCL1; Chemokine CXCL2; Chemotaxis, Leukocyte; Endothelial Cells; Endothelium, Vascular; Gene Expression Profiling; Humans; Interleukin-8; Lectins; Meningitis, Pneumococcal; Mice; Mutation; Neuraminidase; Neutrophil Infiltration; Neutrophils; Oligonucleotide Array Sequence Analysis; Polymerase Chain Reaction; Signal Transduction; Streptococcus pneumoniae

Despite bacteraemia is present in the majority of patients with pneumococcal, little is known about the influence of the systemic infection on the meningeal inflammatory response.. To explore the role of systemic infection on the meningeal inflammation, experimental meningitis was induced by intracisternal injection of approximately 1 x 10(6) CFU Streptococcus pneumoniae, type 3, and the 26 rabbits were either provided with approximately 1 x 10(6) CFU S. pneumoniae intravenously at 0 hour ("bacteraemic" rabbits, n = 9), immunized with paraformaldehyde-killed S. pneumoniae for 5 weeks prior to the experiment ("immunized" rabbits", n = 8), or not treated further ("control" rabbits, n = 9). WBC and bacterial concentrations were determined in CSF and blood every second hour during a 16 hours study period together with CSF IL-8 and protein levels. We also studied CSF and blood WBC levels in 153 pneumococcal meningitis patients with and without presence of bacteraemia.. As designed, blood bacterial concentrations were significantly different among three experimental groups during the 16 hours study period (Kruskal Wallis test, P < 0.05), whereas no differences in CSF bacterial levels were observed (P > 0.05). Blood WBC decreased in bacteraemic rabbits between approximately 10-16 hours after the bacterial inoculation in contrast to an increase for both the immunized rabbits and controls (P < 0.05). The CSF pleocytosis was attenuated in bacteraemic rabbits as compared to the two other groups between 12-16 hours from time of infection (P < 0.017), despite accelerated CSF IL-8 levels in bacteraemic rabbits. In patients with pneumococcal meningitis, no significant difference in CSF WBC was observed between patients with or without bacteraemia at admission (n = 103, 1740 cells/microL (123-4032) vs. n = 50, 1961 cells/microL (673-5182), respectively, P = 0.18), but there was a significant correlation between CSF and blood WBC (n = 127, Spearman rho = 0.234, P = 0.008).. Our results suggest that a decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal meningitis results in an attenuated CSF pleocytosis.

Topics: Animals; Bacteremia; Bacterial Vaccines; Cerebrospinal Fluid; Cerebrospinal Fluid Proteins; Humans; Inflammation; Interleukin-8; Leukocyte Count; Leukocytosis; Meningitis, Pneumococcal; Rabbits; Streptococcus pneumoniae

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

The polysaccharide fucoidin is a selectin blocker that inhibits leukocyte recruitment into the cerebrospinal fluid (CSF) during experimental pneumococcal meningitis. In the present study, the effect of fucoidin treatment on the release of the proinflammatory cytokines tumor necrosis factor alpha (TNF-alpha), interleukin-1 (IL-1), and IL-8 into the CSF was investigated. Rabbits (n = 7) were treated intravenously with 10 mg of fucoidin/kg of body weight every second hour starting 4 h after intracisternal inoculation of approximately 10(6) CFU of Streptococcus pneumoniae type 3 (untreated control group, n = 7). CSF samples were obtained every second hour during a 16-h study period. Treatment with fucoidin caused a consistent and significant decrease in CSF IL-1 levels (in picograms per milliliter) between 12 and 16 h (0 versus 170, 0 versus 526, and 60 versus 1,467, respectively; P < 0.02). A less consistent decrease in CSF TNF-alpha levels was observed in the fucoidin-treated group, but with no significant difference between the two groups (P > 0.05). In contrast, there was no attenuation in CSF IL-8 levels. Indeed, there was a significant increase in CSF IL-8 levels (in picograms per milliliter) in the fucoidin-treated group at 10 and 12 h (921 versus 574 and 1,397 versus 569, respectively; P < 0.09). In conclusion, our results suggest that blood-derived leukocytes mainly are responsible for the release of IL-1 and to some degree TNF-alpha into the CSF during pneumococcal meningitis, whereas IL-8 may be produced by local cells within the brain.

Topics: Animals; Brain; Cerebrospinal Fluid; Chemotaxis, Leukocyte; Cytokines; Injections, Intravenous; Interleukin-1; Interleukin-8; Leukocytosis; Meningitis, Pneumococcal; Polysaccharides; Rabbits; Selectins; Tumor Necrosis Factor-alpha

The role of interleukin (IL)-8 as mediator in the recruitment of leucocytes into the CSF was investigated during experimental pneumococcal meningitis. Rabbits were inoculated intracisternally with approximately 10(6) CFU Streptococcus pneumoniae, and treated (i) intravenously with 5 mg of a monoclonal antibody to IL-8 (n = 7) or 5 mg of an isotype control antibody (n = 6); (ii) intracisternally with anti-IL-8, 100 microg (n = 5), 10 microg (n = 4), 1 microg (n = 4), 0.1 microg (n = 2). Ten rabbits served as untreated control group. Intravenous treatment with anti-IL-8 attenuated the pleocytosis significantly compared to untreated rabbits (P < 0.04) or rabbits treated with an isotype control antibody (P < 0.02). In contrast, intracisternal treatment with anti-IL-8 failed to attenuate the pleocytosis (P > 0.05). These results show, that IL-8 plays an important role in the recruitment of leucocytes during experimental pneumococcal meningitis, and that the functional activity of IL-8 in this process appears to be on the bloodstream side of the microvascular endothelium of the brain.

Topics: Animals; Antibodies, Monoclonal; Brain; Cisterna Magna; Endothelium, Vascular; Injections; Injections, Intravenous; Interleukin-8; Leukocytosis; Meningitis, Pneumococcal; Rabbits