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.
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Hammad A
HA
Ganatra
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Brian M
BM
Varisco
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Kelli
K
Harmon
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Patrick
P
Lahni
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Amy
A
Opoka
Division of Critical Care Medicine, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Hector R
HR
Wong
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use*; D002465:Cell Movement / Q000187:drug effects; D002478:Cells, Cultured; D002648:Child; D016207:Cytokines / Q000097:blood; D004195:Disease Models, Animal; D065206:Extracellular Traps / Q000187:drug effects* / Q000276:immunology; D006801:Humans; D056747:Immunomodulation; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000187:drug effects* / Q000276:immunology / Q000382:microbiology; D051379:Mice; D008810:Mice, Inbred C57BL; D009504:Neutrophils / Q000187:drug effects* / Q000276:immunology; D010529:Peritoneal Cavity / Q000473:pathology*; D009195:Peroxidase / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects; D018805:Sepsis / Q000276:immunology / Q000628:therapy*; D015032:Zinc / Q000627:therapeutic use*
D000893:Anti-Inflammatory Agents; D016207:Cytokines; D018836:Inflammation Mediators; D009195:Peroxidase; D015032:Zinc
Neutrophil extracellular trap; pediatric; sepsis; zinc