title: The causative pathogen determines the inflammatory profile in cerebrospinal fluid and outcome in patients with bacterial meningitis.
abstract: BACKGROUND
  The brain's inflammatory response to the infecting pathogen determines the outcome of bacterial meningitis (BM), for example, the associated mortality and the extent of brain injury. The inflammatory cascade is initiated by the presence of bacteria in the cerebrospinal fluid (CSF) activating resident immune cells and leading to the influx of blood derived leukocytes. To elucidate the pathomechanisms behind the observed difference in outcome between different pathogens, we compared the inflammatory profile in the CSF of patients with BM caused by Streptococcus pneumonia (n = 14), Neisseria meningitidis (n = 22), and Haemophilus influenza (n = 9).
  
  
  METHODS
  CSF inflammatory parameters, including cytokines and chemokines, MMP-9, and nitric oxide synthase activity, were assessed in a cohort of patients with BM from Burkina Faso.
  
  
  RESULTS
  Pneumococcal meningitis was associated with significantly higher CSF concentrations of IFN-γ , MCP-1, and the matrix-metalloproteinase (MMP-) 9. In patients with a fatal outcome, levels of TNF-α, IL-1 β, IL-1RA, IL-6, and TGF-α were significantly higher.
  
  
  CONCLUSIONS
  The signature of pro- and anti-inflammatory mediators and the intensity of inflammatory processes in CSF are determined by the bacterial pathogen causing bacterial meningitis with pneumococcal meningitis being associated with a higher case fatality rate than meningitis caused by N. meningitidis or H. influenzae.
authors.affiliation: Neuroinfection Laboratory, Institute for Infectious Diseases, University of Bern, Friedbuehlstraße 51, 3010 Bern, Switzerland.
authors.forename: Denis
authors.initials: D
authors.lastname: Grandgirard
authors.forename: Rahel
authors.initials: R
authors.lastname: Gäumann
authors.forename: Boubacar
authors.initials: B
authors.lastname: Coulibaly
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Dangy
authors.forename: Ali
authors.initials: A
authors.lastname: Sie
authors.forename: Thomas
authors.initials: T
authors.lastname: Junghanss
authors.forename: Hans
authors.initials: H
authors.lastname: Schudel
authors.forename: Gerd
authors.initials: G
authors.lastname: Pluschke
authors.forename: Stephen L
authors.initials: SL
authors.lastname: Leib
mesh_terms: D000293:Adolescent; D000328:Adult; D002555:Cerebrospinal Fluid / Q000382:microbiology*; D018925:Chemokines / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000378:metabolism; D005260:Female; D006801:Humans; D007223:Infant; D007249:Inflammation / Q000134:cerebrospinal fluid*; D007962:Leukocytes / Q000166:cytology; D008297:Male; D016920:Meningitis, Bacterial / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000382:microbiology*; D008583:Meningitis, Haemophilus / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008585:Meningitis, Meningococcal / Q000134:cerebrospinal fluid / Q000175:diagnosis; D008586:Meningitis, Pneumococcal / Q000134:cerebrospinal fluid / Q000175:diagnosis / Q000382:microbiology; D008875:Middle Aged; D016896:Treatment Outcome; D055815:Young Adult
chemical_list: D018925:Chemokines; D016207:Cytokines