title: A predominantly anti-inflammatory cytokine profile is associated with disease severity in meningococcal sepsis.
abstract: OBJECTIVE
  This study aimed to determine whether an anti-inflammatory profile in meningococcal disease is associated with an increased risk of severe disease or septic shock.
  
  
  METHODS
  Prospective observational study in a tertiary care children's hospital.
  
  
  METHODS
  63 children with confirmed meningococcal disease.
  
  
  METHODS
  Plasma concentrations of interleukin-1 receptor antagonist (IL-1Ra), interleukin-6 (IL-6), interleukin-8 (IL-8) and tumour necrosis factor-alpha (TNF) were assayed on admission. Receiver operator characteristic curve analysis was used to determine optimum thresholds for IL-1Ra:TNF, IL-1Ra:IL-6 and IL-1Ra:IL-8 ratios.
  
  
  RESULTS
  Median IL-1Ra:TNF and IL-1Ra:IL-6 ratios were significantly higher in severe disease with septic shock than in severe disease without septic shock and in non severe disease (IL-1Ra:TNF 263 vs. 185 vs. 108; IL-1Ra:IL-6 139 vs. 23 vs. 17). Median IL-1Ra:IL-8 ratios were not significantly different in the three groups. A significantly larger proportion of children with high IL-1Ra:TNF-alpha and IL-1Ra:IL-6 ratios developed severe disease with septic shock than those with a low ratios (95.2% vs. 4.8%; 76.2% vs. 23.8%).
  
  
  CONCLUSIONS
  An anti-inflammatory profile appears to be associated with the development of severe disease and septic shock in meningococcal sepsis. This may imply that experimental new therapies of pro-inflammatory cytokine inhibition and anti-inflammatory cytokines in meningococcal disease could be detrimental.
authors.affiliation: Wellcome Trust Research Laboratories, Blantyre 3, P.O. Box 30096, Chichiri, Malawi. edcarrol@liv.ac.uk
authors.forename: Enitan D
authors.initials: ED
authors.lastname: Carrol
authors.forename: Alistair P J
authors.initials: AP
authors.lastname: Thomson
authors.forename: Ashley P
authors.initials: AP
authors.lastname: Jones
authors.forename: Graham
authors.initials: G
authors.lastname: Jeffers
authors.forename: C Anthony
authors.initials: CA
authors.lastname: Hart
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D016207:Cytokines / Q000097:blood*; D005260:Female; D006776:Hospitals, Pediatric; D006801:Humans; D007223:Infant; D016015:Logistic Models; D008297:Male; D008581:Meningitis / Q000097:blood* / Q000145:classification / Q000150:complications; D011446:Prospective Studies; D012372:ROC Curve; D012720:Severity of Illness Index; D012772:Shock, Septic / Q000097:blood* / Q000150:complications
chemical_list: D016207:Cytokines