title: Influence of innate cytokine production capacity on clinical manifestation and severity of pediatric meningococcal disease.
abstract: OBJECTIVE
  To analyze the role of the innate production capacity for tumor necrosis factor, interleukin-1beta, interleukin-12, and interleukin-10 in the clinical presentation and severity of meningococcal disease.
  
  
  METHODS
  Whole blood cultures from survivors of severe meningococcal disease obtained median 5.4 yrs after hospitalization were stimulated with meningococcal lipopolysaccharide and heat-killed Neisseria meningitidis bacteria.
  
  
  METHODS
  Intensive care unit in academic hospital.
  
  
  METHODS
  A total of 111 children were included. We classified these patients according to clinical manifestation in four groups: shock (n = 43); both shock and meningitis (n = 11); bacteremia (neither shock nor meningitis, n = 24); and distinct meningitis (n = 33).
  
  
  METHODS
  : None.
  
  
  RESULTS
  The classification into four groups stratifies these patients according to disease severity. No differences in whole blood cytokine production were found between the patients in these four groups. However, within the group of patients who had presented with shock, interleukin-1beta and the interleukin-1beta/interleukin-10 ratio were negatively correlated with disease severity (R = -.35, p = .03 and R = -.33, p = .04, respectively; Pediatric Risk of Mortality score).
  
  
  CONCLUSIONS
  Clinical manifestation of meningococcal disease cannot be explained by the innate production capacity of whole blood cultures for the cytokines tumor necrosis factor, interleukin-1beta, interleukin-10, and interleukin-12. In patients who presented with shock, a low production capacity for interleukin-1beta and a low interleukin-1beta/interleukin-10 production ratio was associated with more severe disease.
authors.affiliation: Department of General Internal Medicine, Nijmegen Institute for Infection, Inflammation and Immunity, Nijmegen, Netherlands. t.sprong@aig.umcn.nl
authors.forename: Tom
authors.initials: T
authors.lastname: Sprong
authors.forename: Johanna
authors.initials: J
authors.lastname: van der Ven-Jongekrijg
authors.forename: Chris
authors.initials: C
authors.lastname: Neeleman
authors.forename: Jos W M
authors.initials: JW
authors.lastname: van der Meer
authors.forename: Marcel
authors.initials: M
authors.lastname: van Deuren
mesh_terms: D000293:Adolescent; D016470:Bacteremia / Q000276:immunology* / Q000401:mortality; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006801:Humans; D007108:Immune Tolerance / Q000276:immunology; D007113:Immunity, Innate / Q000276:immunology*; D007223:Infant; D015278:Intensive Care Units, Pediatric; D016753:Interleukin-10 / Q000097:blood; D018664:Interleukin-12 / Q000097:blood; D053583:Interleukin-1beta / Q000097:blood; D008297:Male; D008585:Meningitis, Meningococcal / Q000175:diagnosis* / Q000276:immunology* / Q000401:mortality; D011379:Prognosis; D012772:Shock, Septic / Q000276:immunology* / Q000401:mortality; D016019:Survival Analysis; D015996:Survival Rate; D018746:Systemic Inflammatory Response Syndrome / Q000276:immunology* / Q000401:mortality; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D016207:Cytokines; D053583:Interleukin-1beta; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D018664:Interleukin-12