Zinc deficiency increases organ damage and mortality in a murine model of polymicrobial sepsis.
OBJECTIVE
Zinc deficiency is common among populations at high risk for sepsis mortality, including elderly, alcoholic, and hospitalized patients. Zinc deficiency causes exaggerated inflammatory responses to endotoxin but has not been evaluated during bacterial sepsis. We hypothesized that subacute zinc deficiency would amplify immune responses and oxidant stress during bacterial sepsis {lsqb;i.e., cecal ligation and puncture (CLP){rsqb; resulting in increased mortality and that acute nutritional repletion of zinc would be beneficial.


METHODS
Prospective, randomized, controlled animal study.


METHODS
University medical center research laboratory.


METHODS
Adult male C57BL/6 mice.


METHODS
Ten-week-old, male, C57BL/6 mice were randomized into three dietary groups: 1) control diet, 2) zinc-deficient diet for 3 weeks, and 3) zinc-deficient diet for 3 weeks followed by oral zinc supplementation for 3 days (n = 35 per diet). Mice were then assigned to receive either CLP or sham operation (n = 15 each per diet). CLP and sham-operated treatment groups were further assigned to a 7-day survival study (n = 10 per treatment per diet) or were evaluated at 24 hours (n = 5 per treatment per diet) for signs of vital organ damage.


RESULTS
Sepsis mortality was significantly increased with zinc deficiency (90% vs. 30% on control diet). Zinc-deficient animals subject to CLP had higher plasma cytokines, more severe organ injury, including increased oxidative tissue damage and cell death, particularly in the lungs and spleen. None of the sham-operated animals died or developed signs of organ damage. Zinc supplementation normalized the inflammatory response, greatly diminished tissue damage, and significantly reduced mortality.


CONCLUSIONS
Subacute zinc deficiency significantly increases systemic inflammation, organ damage, and mortality in a murine polymicrobial sepsis model. Short-term zinc repletion provides significant, but incomplete protection despite normalization of inflammatory and organ damage indices.
Knoell
Daren L
DL
Division of Pulmonary, Allergy, Critical Care, and Sleep Medicine, Dorothy M. Davis Heart and Lung Research Institute, The Ohio State University Medical Center, Columbus, OH, USA.
Julian
Mark W
MW
Bao
Shengying
S
Besecker
Beth
B
Macre
Jennifer E
JE
Leikauf
George D
GD
DiSilvestro
Robert A
RA
Crouser
Elliott D
ED
D000818:Animals; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009102:Multiple Organ Failure / Q000209:etiology* / Q000401:mortality*; D018805:Sepsis / Q000150:complications* / Q000382:microbiology / Q000401:mortality*; D015032:Zinc / Q000172:deficiency*
D015032:Zinc