Effects of endotoxin on zinc metabolism in human volunteers

Abstract

After stress or trauma, the serum zinc concentration decreases. This study evaluated possible mechanisms for hypozincemia with the use of a human endotoxemia model. Two doses of endotoxin [lipopolysaccharide (LPS)] were administered on consecutive mornings to 12 healthy volunteers, and each subject was also studied after saline injection. Blood was analyzed for zinc, cytokines (tumor necrosis factor-alpha and interleukin-6), albumin, albumin-zinc binding, and C-reactive protein (CRP). Serial 24-h urine collections were analyzed for zinc. Each LPS dose briefly increased plasma cytokine concentrations and decreased the serum zinc concentration. Serum albumin, the major zinc binding protein, did not decrease, but a progressive increase in CRP was found. LPS did not alter zinc binding affinity to serum albumin. Urine zinc losses were not increased. We conclude that hypozincemia in this model cannot be explained by decreased serum albumin, changes in serum albumin-zinc binding, or increased urinary zinc excretion. Because hypozincemia was transient and followed cytokine peaks, we postulate that LPS-stimulated hypozincemia is mediated, at least partly, by a cytokine-directed internal redistribution of zinc.

Genome-level expression profiles in pediatric septic shock indicate a role for altered zinc homeostasis in poor outcome

“…Rather, they are more likely to represent an acute redistribution of tissue zinc levels, which may nonetheless represent an acute disruption of zinc homeostasis. This assertion is supported by the work of Gaetke et al (17) involving systemic LPS administration to healthy adult volunteers. These investigators demonstrated acute decreases of serum zinc levels in response to LPS administration.…”

“…1 is biologically plausible and, therefore, provide an important level of confidence in the feasibility of studying clinical pediatric septic shock using a genomic approach based on microarray analysis. Most importantly, the data indicate that within 24 h of presentation to the PICU, children with septic shock are characterized by decreased expression of a large number of genes that either are dependent on zinc homeostasis or play a direct role in zinc homeostasis, an observation that is indirectly supported by the experimental literature (17,24,25,30,37,41) but has not been previously reported at the genomic level and in the setting of clinical pediatric septic shock.…”

Modulated Responses to Restraint Stress and Inflammation in Metallothionein-Null Mice

“…2a). Gaetke et al 24) showed that LPS-injection increased plasma cytokines and decreased serum zinc in humans, and that both the urinary excretion and binding ability to albumin of zinc were not changed. This agrees with our results.…”

Liver Disease

“…Cytokines such as TNF and IL -1 generally cause a decrease in the serum zinc concentration and an internal redistribution of zinc, with zinc being sequestered in the liver and being lost from other tissues such as bone marrow and thymus (Gaetke et al , 1997 ). This internal redistribution of zinc is thought to facilitate priority protein synthesis in the liver, and it also makes the plasma a less favorable environment for bacterial growth (zinc withholding) (Gaetke et al , 1997 ).…”

“…This internal redistribution of zinc is thought to facilitate priority protein synthesis in the liver, and it also makes the plasma a less favorable environment for bacterial growth (zinc withholding) (Gaetke et al , 1997 ). This zinc stress response can also be associated with loss of zinc from critical zinc fi nger proteins and loss of functional activity.…”