title: Sustained elevation of resistin, NGAL and IL-8 are associated with severe sepsis/septic shock in the emergency department.
abstract: OBJECTIVE
  To identify biomarkers which distinguish severe sepsis/septic shock from uncomplicated sepsis in the Emergency Department (ED).
  
  
  METHODS
  Patients with sepsis underwent serial blood sampling, including arrival in the ED and up to three subsequent time points over the first 24 hours. Messenger RNA (mRNA) levels of 13 genes representing arms of the innate immune response, organ dysfunction or shock were measured in peripheral blood leucocytes using quantitative PCR, and compared with healthy controls. Serum protein concentrations of targets differentially expressed between uncomplicated sepsis and severe sepsis/septic shock were then measured at each time point and compared between the two patient groups.
  
  
  RESULTS
  Of 27 participants (median age 66 years, (IQR 35, 78)), 10 had uncomplicated sepsis and 17 had sepsis with organ failure (14 septic shock; 3 had other sepsis-related organ failures). At the time of first sample collection in the ED, gene expression of Interleukin (IL)-10 and Neutrophil Gelatinase Associated Lipocalin (NGAL) were significantly higher in severe sepsis than uncomplicated sepsis. Expression did not significantly change over time for any target gene. Serum concentrations of IL-6, IL-8, IL-10, NGAL and Resistin were significantly higher in severe sepsis than uncomplicated sepsis at the time of first sample collection in the ED, but only IL-8, NGAL and Resistin were consistently higher in severe sepsis compared to uncomplicated sepsis at all time points up to 24 h after presentation.
  
  
  CONCLUSIONS
  These mediators, produced by both damaged tissues and circulating leukocytes, may have important roles in the development of severe sepsis. Further work will determine whether they have any value, in addition to clinical risk parameters, for the early identification of patients that will subsequently deteriorate and/or have a higher risk of death.
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia; Emergency Department, Armadale Health Service, Perth, Australia.
authors.forename: Stephen P J
authors.initials: SP
authors.lastname: Macdonald
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia.
authors.forename: Shelley F
authors.initials: SF
authors.lastname: Stone
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia.
authors.forename: Claire L
authors.initials: CL
authors.lastname: Neil
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia.
authors.forename: Pauline E
authors.initials: PE
authors.lastname: van Eeden
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia; Emergency Department, Royal Perth Hospital, Perth, Australia.
authors.forename: Daniel M
authors.initials: DM
authors.lastname: Fatovich
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia; Emergency Department, Royal Perth Hospital, Perth, Australia.
authors.forename: Glenn
authors.initials: G
authors.lastname: Arendts
authors.affiliation: Centre for Clinical Research in Emergency Medicine, Harry Perkins Institute of Medical Research, Perth, Australia; Discipline of Emergency Medicine, School of Primary, Aboriginal and Rural Health Care, University of Western Australia, Perth, Australia; Emergency Department, Royal Perth Hospital, Perth, Australia.
authors.forename: Simon G A
authors.initials: SG
authors.lastname: Brown
mesh_terms: D000209:Acute-Phase Proteins / Q000235:genetics; D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D018932:Chemokine CCL2 / Q000097:blood; D004636:Emergency Service, Hospital; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood* / Q000235:genetics; D000071068:Lipocalin-2; D054834:Lipocalins / Q000097:blood* / Q000235:genetics; D008297:Male; D008875:Middle Aged; D011518:Proto-Oncogene Proteins / Q000097:blood* / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D052243:Resistin / Q000097:blood* / Q000235:genetics; D012772:Shock, Septic / Q000097:blood* / Q000235:genetics; D013997:Time Factors
chemical_list: D000209:Acute-Phase Proteins; D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D015850:Interleukin-6; D016209:Interleukin-8; C489506:LCN2 protein, human; D000071068:Lipocalin-2; D054834:Lipocalins; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D052243:Resistin; D016753:Interleukin-10