title: A comparison of zinc metabolism, inflammation, and disease severity in critically ill infected and noninfected adults early after intensive care unit admission.
abstract: BACKGROUND
  Zinc deficiency is a cause of immune dysfunction and infection. Previous human studies have shown that the activation of the acute phase response alters zinc metabolism. Whether the alteration in zinc metabolism is predictive of disease severity in the setting of critical illness is unclear.
  
  
  OBJECTIVE
  We sought to determine whether differences occur in zinc metabolism at the onset of critical illness between infected (septic) and noninfected subjects.
  
  
  METHODS
  We conducted this prospective study in an adult medical intensive care unit (MICU) at a tertiary care hospital. Subjects were enrolled within 24 h of intensive care unit admission. Subjects who did not meet sepsis criteria were considered for the critically ill control (CIC) arm. After patient consent, blood was immediately collected to measure plasma zinc and cytokine concentrations and zinc transporter gene expression in peripheral blood monocytes. Clinical data during the MICU stay were also recorded.
  
  
  RESULTS
  A total of 56 patients were evaluated (22 septic, 22 CIC, and 12 healthy subjects). Plasma zinc concentrations were below normal in CIC patients and further reduced in the septic cohort (57.2 ± 18.2 compared with 45.5 ± 18.1 μg/dL). Cytokine concentrations increased with decreasing plasma zinc concentrations (P = 0.05). SLC39A8 gene expression was highest in patients with the lowest plasma zinc concentrations and the highest severity of illness.
  
  
  CONCLUSIONS
  The alteration of zinc metabolism was more pronounced in septic patients than in noninfected critically ill patients. Specifically, sepsis was associated with lower plasma zinc concentrations and higher SLC39A8 mRNA expression, which correlated with an increased severity of illness, including cardiovascular dysfunction.
authors.affiliation: Division of Pulmonary, Critical Care and Sleep Medicine and Human Nutrition, The Ohio State University Medical Center, Columbus, OH 43210, USA. beth.besecker@osumc.edu
authors.forename: Beth Y
authors.initials: BY
authors.lastname: Besecker
authors.forename: Matthew C
authors.initials: MC
authors.lastname: Exline
authors.forename: Jennifer
authors.initials: J
authors.lastname: Hollyfield
authors.forename: Gary
authors.initials: G
authors.lastname: Phillips
authors.forename: Robert A
authors.initials: RA
authors.lastname: Disilvestro
authors.forename: Mark D
authors.initials: MD
authors.lastname: Wewers
authors.forename: Daren L
authors.initials: DL
authors.lastname: Knoell
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D027682:Cation Transport Proteins / Q000235:genetics / Q000378:metabolism*; D016638:Critical Illness; D016207:Cytokines / Q000097:blood*; D005260:Female; D015870:Gene Expression; D006801:Humans; D007249:Inflammation / Q000097:blood*; D007362:Intensive Care Units; D008297:Male; D008875:Middle Aged; D011446:Prospective Studies; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D018805:Sepsis / Q000097:blood* / Q000145:classification / Q000378:metabolism; D012720:Severity of Illness Index; D055815:Young Adult; D015032:Zinc / Q000097:blood / Q000172:deficiency*
chemical_list: D027682:Cation Transport Proteins; D016207:Cytokines; D012333:RNA, Messenger; C530151:SLC39A8 protein, human; D015032:Zinc