title: Influence of the blood bacterial load on the meningeal inflammatory response in Streptococcus pneumoniae meningitis.
abstract: BACKGROUND
  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.
  
  
  METHODS
  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.
  
  
  RESULTS
  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).
  
  
  CONCLUSIONS
  Our results suggest that a decrease in peripheral WBC induced by enhanced bacteraemia in pneumococcal meningitis results in an attenuated CSF pleocytosis.
authors.affiliation: Division of Microbiology, National Center for Antimicrobials and Infection Control, Statens Serum Institut, Copenhagen, Denmark. coa@ssi.dk
authors.forename: Christian
authors.initials: C
authors.lastname: Østergaard
authors.forename: Terence
authors.initials: T
authors.lastname: O'Reilly
authors.forename: Christian
authors.initials: C
authors.lastname: Brandt
authors.forename: Niels
authors.initials: N
authors.lastname: Frimodt-Møller
authors.forename: Jens D
authors.initials: JD
authors.lastname: Lundgren
mesh_terms: D000818:Animals; D016470:Bacteremia / Q000097:blood / Q000134:cerebrospinal fluid / Q000382:microbiology*; D001428:Bacterial Vaccines / Q000008:administration & dosage; D002555:Cerebrospinal Fluid / Q000166:cytology / Q000382:microbiology; D002556:Cerebrospinal Fluid Proteins / Q000134:cerebrospinal fluid; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000382:microbiology; D016209:Interleukin-8 / Q000134:cerebrospinal fluid; D007958:Leukocyte Count; D007964:Leukocytosis / Q000134:cerebrospinal fluid; D008586:Meningitis, Pneumococcal / Q000097:blood / Q000134:cerebrospinal fluid / Q000276:immunology / Q000473:pathology*; D011817:Rabbits; D013296:Streptococcus pneumoniae / Q000276:immunology* / Q000472:pathogenicity*
chemical_list: D001428:Bacterial Vaccines; D002556:Cerebrospinal Fluid Proteins; D016209:Interleukin-8