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Updated: May 20, 2026
A Controlled Mouse Model for Neonatal Polymicrobial Sepsis
Published on: January 27, 2019
Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis
Jeffrey E Nowak1, Kelli Harmon, Charles C Caldwell
1Department of Pediatrics, Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center and Cincinnati Children's Research Foundation, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Insights
Prophylactic zinc supplementation improved survival in a murine sepsis model by reducing bacterial load and enhancing immune cell function. This suggests zinc may be a potential therapeutic agent for sepsis.
Area of Science:
- Immunology
- Microbiology
- Nutritional Science
Background:
- Altered zinc homeostasis is a key feature of pediatric sepsis.
- Zinc supplementation presents a potential therapeutic strategy for sepsis.
Purpose of the Study:
- To test the hypothesis that prophylactic zinc supplementation benefits a murine model of peritoneal sepsis.
- To evaluate the impact of zinc supplementation on survival, inflammation, and bacterial load in sepsis.
Main Methods:
- A murine model of peritoneal sepsis was established using intraperitoneal fecal-slurry injection.
- Mice received prophylactic zinc gluconate supplementation (10 mg/kg) for 3 days prior to sepsis induction.
- Outcomes measured included survival, inflammatory markers, bacterial load, and macrophage phagocytosis.
Main Results:
- Zinc-supplemented mice showed a significant survival advantage over control mice.
- Supplementation led to moderate reductions in inflammation and immune activation.
- Survival benefit correlated with reduced in vivo bacterial load and enhanced macrophage phagocytosis of bacteria.
Conclusions:
- Prophylactic zinc supplementation is beneficial in a murine model of peritoneal sepsis.
- Zinc supplementation effectively reduces bacterial load and enhances immune defense mechanisms.
Objective:
We previously demonstrated that altered zinc homeostasis is an important feature of pediatric sepsis, thus raising the possibility of zinc supplementation as a therapeutic strategy in sepsis. Herein, we tested the hypothesis that prophylactic zinc supplementation would be beneficial in a murine model of peritoneal sepsis.
Design:
Murine model of sepsis (intraperitoneal fecal-slurry injection).
Setting:
Basic science research laboratory.
Subjects:
C57BL/6 male mice.
Interventions:
Intraperitoneal fecal-slurry injection, with or without zinc supplementation (10 mg/kg of intraperitoneal zinc gluconate for 3 days prior to intraperitoneal fecal-slurry injection).
Measurements And Main Results:
Survival over 3 days following intraperitoneal fecal-slurry injection, markers of inflammation, bacterial load studies, and immunophenotyping studies. Zinc-supplemented mice demonstrated a significant survival advantage compared to control (nonsupplemented) mice. Zinc-supplemented mice also demonstrated moderate reductions of inflammation and immune activation. The survival advantage primarily correlated with reduced in vivo bacterial load in zinc-supplemented mice, compared to controls. In addition, peritoneal macrophages harvested from zinc-supplemented mice demonstrated a significantly enhanced phagocytosis capacity for Escherichia coli and Staphylococcus aureus, compared to peritoneal macrophages harvested from control mice.
Conclusion:
Prophylactic zinc supplementation reduces bacterial load and is beneficial in a murine model of peritoneal sepsis.
