title: Cytokine activation through sublethal hemorrhage is protective against early lethal endotoxic challenge.
abstract: OBJECTIVE
  To determine the immunologic consequences of nonlethal hemorrhage on subsequent exposure to lipopolysaccharide (LPS) and to determine the role of interleukin 1 beta (IL-1) specifically in mediating the response to LPS with and without prior hemorrhage.
  
  
  METHODS
  Prospective, randomized, controlled experimental trial.
  
  
  METHODS
  Male BALB/c mice and transgenic mice deficient in IL-1 converting enzyme.
  
  
  METHODS
  Animals were subjected to hemorrhage (by cardiac puncture), LPS challenge by intraperitoneal injection, or hemorrhage followed 24 hours later by LPS challenge. Mortality was assessed every 4 hours for 96 hours following hemorrhage or LPS exposure. Serum IL-1 levels were determined 24 hours after exposure to hemorrhage and LPS.
  
  
  METHODS
  University of South Florida Core General Surgery Research Facility, Tampa.
  
  
  METHODS
  Mortality and serum IL-1 levels.
  
  
  RESULTS
  Hemorrhage alone resulted in complete survival, whereas LPS alone resulted in near-complete (95%) mortality. Hemorrhage, when given 24 hours before LPS challenge, afforded significant protection compared with LPS alone (67% survival vs 5% survival; P < .001). Serum IL-1 levels 24 hours after exposure to LPS were significantly lower in prehemorrhaged mice than in those receiving LPS alone. Transgenic mice incapable of producing biologically active IL-1 were further protected, demonstrating near-complete (95%) survival following hemorrhage and LPS challenge.
  
  
  CONCLUSIONS
  Cytokine activation through nonlethal hemorrhage attenuates subsequent IL-1 response to early immunologic challenge. Such immune suppression appears to be protective early on and is supported by the near-complete immunity to LPS in animals incapable of producing biologically active IL-1.
authors.affiliation: Department of Surgery, University of South Florida, Tampa, USA.
authors.forename: E E
authors.initials: EE
authors.lastname: Zervos
authors.forename: J G
authors.initials: JG
authors.lastname: Norman
authors.forename: D W
authors.initials: DW
authors.lastname: Denham
authors.forename: L C
authors.initials: LC
authors.lastname: Carey
authors.forename: D
authors.initials: D
authors.lastname: Livingston
authors.forename: A S
authors.initials: AS
authors.lastname: Rosemurgy
mesh_terms: D000818:Animals; D006470:Hemorrhage / Q000276:immunology* / Q000401:mortality; D007375:Interleukin-1 / Q000276:immunology*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D016019:Survival Analysis
chemical_list: D007375:Interleukin-1; D008070:Lipopolysaccharides