title: Plasma fractalkine is a sustained marker of disease severity and outcome in sepsis patients.
abstract: BACKGROUND
  Fractalkine is a chemokine implicated as a mediator in a variety of inflammatory conditions. Knowledge of fractalkine release in patients presenting with infection to the Intensive Care Unit (ICU) is highly limited. The primary objective of this study was to establish whether plasma fractalkine levels are elevated in sepsis and associate with outcome. The secondary objective was to determine whether fractalkine can assist in the diagnosis of infection upon ICU admission.
  
  
  METHODS
  Fractalkine was measured in 1103 consecutive sepsis patients (including 271 patients with community-acquired pneumonia (CAP)) upon ICU admission and at days 2 and 4 thereafter; in 73 ICU patients treated for suspected CAP in whom this diagnosis was refuted in retrospect; and in 5 healthy humans intravenously injected with endotoxin.
  
  
  RESULTS
  Compared to healthy volunteers, sepsis patients had strongly elevated fractalkine levels. Fractalkine levels increased with the number of organs failing, were higher in patients presenting with shock, but did not vary by site of infection. Non-survivors had sustained elevated fractalkine levels when compared to survivors. Fractalkine was equally elevated in CAP patients and patients treated for CAP but in whom the diagnosis was retrospectively refuted. Fractalkine release induced by intravenous endotoxin followed highly similar kinetics as the endothelial cell marker E-selectin.
  
  
  CONCLUSIONS
  Plasma fractalkine is an endothelial cell derived biomarker that, while not specific for infection, correlates with disease severity in sepsis patients admitted to the ICU.
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. a.j.hoogendijk@amc.uva.nl.
authors.forename: Arie J
authors.initials: AJ
authors.lastname: Hoogendijk
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. m.a.wiewel@amc.uva.nl.
authors.forename: Maryse A
authors.initials: MA
authors.lastname: Wiewel
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. l.a.vanvught@amc.uva.nl.
authors.forename: Lonneke A
authors.initials: LA
authors.lastname: van Vught
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. b.scicluna@amc.uva.nl.
authors.forename: Brendon P
authors.initials: BP
authors.lastname: Scicluna
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. hakima1212@hotmail.com.
authors.forename: Hakima
authors.initials: H
authors.lastname: Belkasim-Bohoudi
authors.affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. j.horn@amc.uva.nl.
authors.forename: Janneke
authors.initials: J
authors.lastname: Horn
authors.affiliation: Clinical Epidemiology Biostatistics and Bioinformatics, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. a.h.zwinderman@amc.uva.nl.
authors.forename: Aeilko H
authors.initials: AH
authors.lastname: Zwinderman
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. p.m.c.kleinklouwenberg@umcutrecht.nl.|Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. p.m.c.kleinklouwenberg@umcutrecht.nl.
authors.forename: Peter M C
authors.initials: PM
authors.lastname: Klein Klouwenberg
authors.affiliation: Department of Intensive Care Medicine, University Medical Center Utrecht, Utrecht, The Netherlands. o.l.cremer@umcutrecht.nl.
authors.forename: Olaf L
authors.initials: OL
authors.lastname: Cremer
authors.affiliation: Department of Medical Microbiology, University Medical Center Utrecht, Utrecht, The Netherlands. m.j.m.bonten@umcutrecht.nl.|Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands. m.j.m.bonten@umcutrecht.nl.
authors.forename: Marc J
authors.initials: MJ
authors.lastname: Bonten
authors.affiliation: Department of Intensive Care, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. marcus.j.schultz@gmail.com.
authors.forename: Marcus J
authors.initials: MJ
authors.lastname: Schultz
authors.affiliation: Center for Experimental and Molecular Medicine, Academic Medical Center, University of Amsterdam, Meibergdreef 9, G2-130, 1105 AZ, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl.|Division of Infectious Diseases, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands. t.vanderpoll@amc.uva.nl.
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000032:analysis / Q000097:blood; D054428:Chemokine CX3CL1 / Q000032:analysis* / Q000097:blood; D005260:Female; D006801:Humans; D007362:Intensive Care Units / Q000706:statistics & numerical data; D008297:Male; D008875:Middle Aged; D063868:Patient Outcome Assessment; D011379:Prognosis; D018805:Sepsis / Q000097:blood / Q000175:diagnosis* / Q000401:mortality; D012720:Severity of Illness Index
chemical_list: D015415:Biomarkers; D054428:Chemokine CX3CL1