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

Jeffrey E Nowak, Kelli Harmon, Charles C Caldwell, Hector R Wong

Index: Pediatr. Crit. Care Med. 13(5) , e323-9, (2012)

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Abstract

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.