title: Severe bacteremia results in a loss of hepatic bacterial clearance.
abstract: BACKGROUND
  Although it has been postulated that liver injury results in impaired clearance of bacteria from the blood, no prior study has evaluated hepatic bacterial clearance during sepsis.
  
  
  OBJECTIVE
  We hypothesized that liver injury during the evolution of sepsis would result in impaired hepatic bacterial clearance.
  
  
  METHODS
  Mild and severe bacteremia were generated in C57BL/6 mice by low- and high-dose intratracheal inoculation with Pseudomonas aeruginosa.
  
  
  RESULTS
  The mortality rates with mild and severe bacteremia were 20% and 60%, respectively. Hepatic bacterial clearance was preserved throughout the evolution of mild bacteremia but was lost late with severe bacteremia. The loss of hepatic bacterial clearance resulted in increased systemic bacteremia and mortality. Pretreatment with a caspase inhibitor resulted in preservation of hepatic bacterial clearance with severe bacteremia and eventual control of the bacteremia. When Kupffer cells were ablated before the onset of bacteremia, there was a loss of hepatic bacterial clearance. This converted an initially mild bacteremia into severe bacteremia with increased organ injury and mortality.
  
  
  CONCLUSIONS
  These observations suggest that hepatic bacterial clearance may be lost during the evolution of sepsis, resulting in a failure to control bacteremia. Thus, the capacity of the liver to clear bacteria is an important determinant of the outcome in sepsis.
authors.affiliation: Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, C-33 GH, Iowa City, IA 52242, USA. alix-ashare@uiowa.edu
authors.forename: Alix
authors.initials: A
authors.lastname: Ashare
authors.forename: Martha M
authors.initials: MM
authors.lastname: Monick
authors.forename: Linda S
authors.initials: LS
authors.lastname: Powers
authors.forename: Timur
authors.initials: T
authors.lastname: Yarovinsky
authors.forename: Gary W
authors.initials: GW
authors.lastname: Hunninghake
mesh_terms: D000818:Animals; D000907:Antibodies, Bacterial / Q000032:analysis; D017209:Apoptosis; D016470:Bacteremia / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D004269:DNA, Bacterial / Q000032:analysis; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D007728:Kupffer Cells / Q000473:pathology; D008099:Liver / Q000382:microbiology*; D008107:Liver Diseases / Q000209:etiology* / Q000473:pathology; D051379:Mice; D008810:Mice, Inbred C57BL; D016133:Polymerase Chain Reaction; D011379:Prognosis; D011552:Pseudomonas Infections / Q000150:complications* / Q000382:microbiology / Q000473:pathology; D011550:Pseudomonas aeruginosa / Q000235:genetics / Q000276:immunology / Q000302:isolation & purification; D012720:Severity of Illness Index
chemical_list: D000907:Antibodies, Bacterial; D004269:DNA, Bacterial