Prophylactic zinc supplementation reduces bacterial load and improves survival in a murine model of sepsis

• Published in: Pediatric critical care medicine Vol. 13; no. 5; p. e323
• Main Authors: Nowak, Jeffrey E, Harmon, Kelli, Caldwell, Charles C, Wong, Hector R
• Format: Journal Article
• Language: English
• Published: United States 01.09.2012
• Subjects: Animals; Bacterial Load - drug effects; Disease Models, Animal; Feces; Gluconates - immunology; Gluconates - therapeutic use; Macrophages, Peritoneal - drug effects; Male; Mice; Mice, Inbred C57BL; Peritonitis - complications; Peritonitis - microbiology; Peritonitis - prevention & control; Phagocytosis - drug effects; Sepsis - microbiology; Sepsis - prevention & control; Survival Rate; Trace Elements - therapeutic use
• ISSN: 1529-7535
• DOI: 10.1097/PCC.0b013e31824fbd90

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. Murine model of sepsis (intraperitoneal fecal-slurry injection). Basic science research laboratory. C57BL/6 male mice. 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). 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. Prophylactic zinc supplementation reduces bacterial load and is beneficial in a murine model of peritoneal sepsis.