title: Multiple system organ failure may be influenced by macrophage hypoactivation as well as hyperactivation--importance of the double challenge.
abstract: OBJECTIVE
  To find out if an infective challenge caused by a burn followed by caecal ligation and puncture in mice caused more abnormalities of the immune response than burn alone or caecal ligation and puncture alone.
  
  
  METHODS
  Laboratory study.
  
  
  METHODS
  University hospital, USA.
  
  
  METHODS
  80 male 7-8 week old A/J mice.
  
  
  METHODS
  Burn followed 10 days later by caecal ligation and puncture (n = 18), caecal ligation and puncture alone (n = 24), burn alone (n = 20), and controls (n = 18). The mice had their spleens removed on day 11 (n = 28; 6, 8, 8, and 6 in the respective groups), day 12 (n = 26; 6, 8, 6, and 6), and day 13 (n = 26; 6, 8, 6, and 6), and splenocytes and adherent cells were harvested for measurement of prostaglandin E2 (PGE2), interleukin 1 (IL-1), interleukin 2 (IL-2), interleukin 6 (IL-6), and tumour necrosis factor alpha (TNF-alpha).
  
  
  METHODS
  Alterations in the production of the cytokines.
  
  
  RESULTS
  After the double challenge (burn followed by caecal ligation and puncture) there were significant reductions in production of TNF-alpha and IL-6 compared with caecal ligation and puncture alone (p < 0.05), burn alone (p < 0.05), and controls (p < 0.05). These findings indicate that activation of macrophages was reduced after infection; production of TNF-alpha, IL-1, and IL-6 by splenocytes stimulated by lipopolysaccharide was reduced.
  
  
  CONCLUSIONS
  The differences do not seem big enough to indicate that mortality would be increased after caecal ligation and puncture alone. Only when there has been a previous injury (which resulted in hyperactivation of macrophages followed by a more pronounced hypoactivation) would mortality increase. In view of clinical trials with antiendotoxin and antiTNF antibodies that failed to improve survival in infected patients, we suggest that the mechanisms of the cellular immune response need further clarification.
authors: Department of Surgery, Brigham and Womens Hospital, Harvard University Medical School, Boston, MA, USA.
authors: R G
authors: RG
authors: Holzheimer
authors: R
authors: R
authors: Molloy
authors: M V
authors: MV
authors: Mendez
authors: D
authors: D
authors: O'Riordain
authors: P
authors: P
authors: Curley
authors: M
authors: M
authors: Nestor
authors: K
authors: K
authors: Collins
authors: I
authors: I
authors: Saproschetz
authors: J A
authors: JA
authors: Mannick
authors: M L
authors: ML
authors: Rodrick
mesh_terms: D000818:Animals; D002056:Burns / Q000276:immunology; D007111:Immunity, Cellular; D007376:Interleukin-2 / Q000096:biosynthesis; D008262:Macrophage Activation / Q000276:immunology*; D008297:Male; D051379:Mice; D008805:Mice, Inbred A; D009102:Multiple Organ Failure / Q000276:immunology*; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis
chemical_list: D007376:Interleukin-2; D014409:Tumor Necrosis Factor-alpha