This Article Full Text Full Text (PDF) All Versions of this Article: 200509-1470OCv1 173/6/644    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Ashare, A. Articles by Hunninghake, G. W. Search for Related Content PubMed PubMed Citation Articles by Ashare, A. Articles by Hunninghake, G. W.

Severe Bacteremia Results in a Loss of Hepatic Bacterial Clearance

Division of Pulmonary and Critical Care and Occupational Medicine, Department of Internal Medicine, University of Iowa College of Medicine; and Veteran's Administration Medical Center, Iowa City, Iowa

Correspondence and requests for reprints should be addressed to Alix Ashare, M.D., Division of Pulmonary, Critical Care, and Occupational Medicine, University of Iowa College of Medicine, 200 Hawkins Drive, C-33 GH, Iowa City, IA 52242. E-mail: alix-ashare{at}uiowa.edu

Rationale: 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.

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 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.

Key Words: apoptosis • bacteremia • infection

This article has been cited by other articles:

				A. Ashare, A. B. Nymon, K. C. Doerschug, J. M. Morrison, M. M. Monick, and G. W. Hunninghake Insulin-like Growth Factor-1 Improves Survival in Sepsis via Enhanced Hepatic Bacterial Clearance Am. J. Respir. Crit. Care Med., July 15, 2008; 178(2): 149 - 157. [Abstract] [Full Text] [PDF]

				A. Ashare, M. M. Monick, A. B. Nymon, J. M. Morrison, M. Noble, L. S. Powers, T. O. Yarovinsky, T. L. Yahr, and G. W. Hunninghake Pseudomonas aeruginosa Delays Kupffer Cell Death via Stabilization of the X-Chromosome-Linked Inhibitor of Apoptosis Protein J. Immunol., July 1, 2007; 179(1): 505 - 513. [Abstract] [Full Text] [PDF]

				E. B. Milbrandt, A. Ishizaka, and D. C. Angus Update in Critical Care 2006 Am. J. Respir. Crit. Care Med., April 1, 2007; 175(7): 638 - 648. [Full Text] [PDF]