EFFECTS OF ENDOTOXIN ON ZINC-METABOLISM IN HUMAN VOLUNTEERS

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