Zinc supplementation leads to immune modulation and improved survival in a juvenile model of murine sepsis.

Children with severe sepsis are known to have altered zinc homeostasis and decreased circulating zinc levels, suggesting a role for zinc supplementation to improve outcomes. We tested the hypothesis that zinc supplementation would improve survival in a juvenile model of polymicrobial sepsis. Juvenile (13-14-d-old) C57BL/6 mice were treated with 10 mg/kg of zinc via i.p. injections (or vehicle) for 3 d prior to induction of polymicrobial sepsis via i.p. cecal slurry injections. Survival after sepsis was followed for 3 d, and bacterial clearance, ex vivo phagocytosis, systemic inflammatory markers and neutrophil extracellular trap (NET) formation were quantified. We found a significant survival benefit and decreased bacterial burden among zinc supplemented mice when compared with the control group. Zinc supplementation also resulted in enhanced phagocytic activity, greater neutrophil recruitment in the peritoneal cavity and NET formation, suggesting a possible mechanism for improved bacterial clearance and survival. We also noted decreased serum cytokine levels and decreased myeloperoxidase activity in lung tissue following zinc supplementation, suggesting attenuation of the systemic inflammatory response. In conclusion, zinc supplementation improves bacterial clearance, and hence survival, in juvenile mice with polymicrobial sepsis.

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

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.