title: Plasma interferon-gamma and interleukin-10 concentrations in systemic meningococcal disease compared with severe systemic Gram-positive septic shock.
abstract: OBJECTIVE
  To analyze plasma interferon-gamma and interleukin-10 concentrations in patients with systemic meningococcal disease and patients with severe Gram-positive septic shock caused by Streptococcus pneumoniae or Staphylococcus aureus. To study the in vitro cytokine (interferon-gamma and interleukin-10) responses in a whole blood model boosted with heat-killed Neisseria meningitidis, S. pneumoniae, and S. aureus before and after treatment with recombinant interleukin-10 or recombinant interferon-gamma.
  
  
  METHODS
  Experimental study.
  
  
  METHODS
  Laboratory.
  
  
  METHODS
  Plasma samples were collected from patients with systemic meningococcal disease (n = 66) and patients with severe Gram-positive septic shock caused by S. pneumoniae (n = 4) or S. aureus (n = 3).
  
  
  METHODS
  Whole blood was boosted with heat-killed N. meningitidis, S. pneumoniae, and S. aureus (1 x 106 colony forming units/mL), and plasmas were analyzed for interleukin-10 or interferon-gamma at 0, 5, 12, and 24 hrs. Furthermore, recombinant interleukin-10 or recombinant interferon-gamma was added before bacteria, and the effect on the secretion of interferon-gamma and interleukin-10, respectively, was analyzed after 24 hrs.
  
  
  RESULTS
  The median concentration of interferon-gamma was 15 pg/mL and of interleukin-10 was 10,269 pg/mL in patients with meningococcal septic shock (n = 24) compared with median interferon-gamma concentration of 3400 pg/mL and interleukin-10 concentration of 465 pg/mL in patients with severe Gram-positive shock (p =.001). Increased interferon-gamma concentrations were associated with case fatality (p =.011). In a whole blood model we demonstrated that 1 x 106 colony forming units/mL of N. meningitidis induced more interleukin-10 but less interferon-gamma than S. pneumoniae. S. aureus induced minimal secretion of both cytokines. Recombinant interleukin-10 efficiently down-regulated the secretion of interferon-gamma, and vice versa, as shown in a whole blood model.
  
  
  CONCLUSIONS
  We speculate whether high concentrations of interleukin-10 contribute to the low concentrations of interferon-gamma in fulminant meningococcal septicemia. In addition, it appears as if interferon-gamma plays a minor role in the pathophysiology of meningococcal septic shock.
authors.affiliation: Department of Clinical Chemistry, Ullevål University Hospital, Oslo, Norway.
authors.forename: Anna
authors.initials: A
authors.lastname: Bjerre
authors.forename: Berit
authors.initials: B
authors.lastname: Brusletto
authors.forename: Ernst Arne
authors.initials: EA
authors.lastname: Høiby
authors.forename: Peter
authors.initials: P
authors.lastname: Kierulf
authors.forename: Petter
authors.initials: P
authors.lastname: Brandtzaeg
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D002648:Child; D002675:Child, Preschool; D016908:Gram-Positive Bacterial Infections / Q000097:blood*; D006801:Humans; D007223:Infant; D007371:Interferon-gamma / Q000097:blood*; D016753:Interleukin-10 / Q000097:blood*; D008589:Meningococcal Infections / Q000097:blood*; D008875:Middle Aged; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood*
chemical_list: D016753:Interleukin-10; D007371:Interferon-gamma