Related Experiment Video
Updated: Aug 13, 2026
A Neonatal Imaging Model of Gram-Negative Bacterial Sepsis
Published on: August 12, 2020
Severe bacteremia results in a loss of hepatic bacterial clearance
Alix Ashare1, Martha M Monick, Linda S Powers
1Division 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
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.
Insights
Liver injury impairs bacterial clearance during sepsis, increasing mortality. Protecting hepatic bacterial clearance, potentially via caspase inhibitors or Kupffer cells, improves sepsis outcomes.
Area of Science:
- Sepsis research
- Hepatology
- Immunology
Background:
- Liver injury is suspected to impair bacterial clearance from the blood.
- No previous studies investigated hepatic bacterial clearance during sepsis progression.
Purpose of the Study:
- To test the hypothesis that liver injury during sepsis impairs hepatic bacterial clearance.
- To determine the role of hepatic bacterial clearance in sepsis outcome.
Main Methods:
- Induced mild and severe bacteremia in C57BL/6 mice using Pseudomonas aeruginosa.
- Evaluated hepatic bacterial clearance, mortality rates, and the effects of caspase inhibitors and Kupffer cell ablation.
Main Results:
- Mortality rates were 20% (mild bacteremia) and 60% (severe bacteremia).
- Hepatic bacterial clearance was maintained in mild sepsis but lost in severe sepsis, correlating with increased bacteremia and mortality.
- Caspase inhibition preserved clearance in severe sepsis; Kupffer cell ablation impaired clearance, worsening sepsis severity and outcomes.
Conclusions:
- Hepatic bacterial clearance can be lost during sepsis, leading to uncontrolled bacteremia and increased mortality.
- The liver's capacity to clear bacteria is a critical factor in determining sepsis outcomes.
Related Concept Videos
01:26Effect of Hepatic Disease on Pharmacokinetics: Drug Dosing and Hepatic Blood Flow
01:09Hepatic Drug Clearance: Restrictive and Nonrestrictive Clearance
Most drugs undergo restrictive clearance, which is proportional to the...
01:09Hepatic Drug Clearance: Effect of Protein Binding
For low-extraction-ratio drugs that are less than 80% protein-bound, minor changes in protein binding...
01:17Chronic Bowel Disorders: Introduction
Irritable Bowel Syndrome (IBS) is a common disorder affecting the gastrointestinal tract. The distinctive feature is recurrent abdominal pain associated with altered bowel movements, manifesting as constipation, diarrhea, or fluctuating between both. The...
01:27Inflammatory Bowel Disease I: Ulcerative Colitis
Inflammatory bowel disease, or IBD, encompasses a group of disorders characterized by chronic inflammation or ulceration of the gastrointestinal tract.
Risk Factors
The exact cause of IBD remains unclear, although it is believed to be due to a mix of genetic, environmental, microbial, and immune factors. Genetic factors are significant in determining susceptibility to IBD, with family history being a critical risk factor. Individuals with a first-degree relative who has IBD are at...
01:31Defense Against Bacterial Pathogens
Phagocytes
Phagocytes are the frontline soldiers of the immune system. They include neutrophils and macrophages. Neutrophils are the most abundant type of white blood cell and are quickly mobilized to the site of infection. Macrophages are larger cells that patrol...