Published ahead of print on January 6, 2006, doi:10.1164/rccm.200509-1470OC Am. J. Respir. Crit. Care Med., Volume 173, Number 6, March 2006, 644-652 A more recent version of this article appeared on March 15, 2006
Submitted on September 20, 2005 Severe Bacteremia Results in a Loss of Hepatic Bacterial ClearanceAlix Ashare1*,1 Department of Internal Medicine, Division of Pulmonary and Critical Care and Occupational Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA, 2 Department of Internal Medicine, Division of Pulmonary and Critical Care and Occupational Medicine, University of Iowa College of Medicine, Iowa City, Iowa, USA; Veteran's Administration Medical Center, Iowa City, Iowa, USA * To whom correspondence should be addressed. E-mail: alix-ashare{at}uiowa.edu.
Rationale: While it has been postulated that liver injury results in impaired clearance of bacteria from the blood, no prior study has directly evaluated hepatic bacterial clearance during sepsis. Objectives: 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. Measurements and Main Results: The mortality with mild and severe bacteremia was 20% and 60%, respectively. Hepatic bacterial clearance was preserved throughout the evolution of mild bacteremia, but lost late with severe bacteremia. The loss of hepatic bacterial clearance resulted in increased systemic bacteremia and mortality. Pre-treatment 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 prior to the onset of bacteremia, there was a loss of hepatic bacterial clearance. This converted an initial 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. Key words: Apoptosis, Bacteremia, Infection
This article has been cited by other articles:
|
|
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
