title: Serum Levels of TNF Receptor Ligands Are Dysregulated in Sepsis and Predict Mortality in Critically Ill Patients.
abstract: TNF superfamily members, including TNF-related weak inducer of apoptosis (TWEAK) and Glucocorticoid-Induced TNFR-Related Protein Ligand (GITRL) have been described as serum based biomarkers for inflammatory and immune mediated diseases. However, up to now the role of TWEAK and GITRL has not been analyzed in critical illness and sepsis.
  
  
  
  GITRL and TWEAK serum concentrations were measured in 121 critically ill patients (84 fulfilled with septic disease), in comparison to 50 healthy controls. Results were correlated with clinical data.
  
  
  
  Serum levels of TWEAK and GITRL were strongly decreased in critically ill patients compared with healthy controls. Concentrations of TWEAK (but not GITRL) were further decreased in patients with sepsis and correlated with routinely used markers of inflammation and bacterial infection such as C-reactive protein, procalcitonin and Interleukin-6. Notably, we failed to detect a correlation to other TNFR ligands such as TNF or APRIL. Finally, TWEAK levels of the upper quartile of the cohort were prognostic for mortality during ICU treatment.
  
  
  
  TWEAK and GITRL levels were lower in intensive care unit medical patients. Levels of TWEAK were further decreased in septic patients, and alterations in TWEAK concentrations were linked to an unfavorable outcome. Together with recently published results on other TNFR ligands, these data indicate specific functions of the different TNFR ligands in septic diseases.
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Roderburg
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Fabian
authors.initials: F
authors.lastname: Benz
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Florian
authors.initials: F
authors.lastname: Schüller
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Ines
authors.initials: I
authors.lastname: Pombeiro
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany.
authors.forename: Hans-Joerg
authors.initials: HJ
authors.lastname: Hippe
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany.
authors.forename: Norbert
authors.initials: N
authors.lastname: Frey
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Christian
authors.initials: C
authors.lastname: Trautwein
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Tom
authors.initials: T
authors.lastname: Luedde
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Alexander
authors.initials: A
authors.lastname: Koch
authors.affiliation: Department of Medicine III, University Hospital RWTH Aachen, Pauwelsstrasse 30, 52074, Aachen, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Tacke
authors.affiliation: Department of Internal Medicine III, University of Kiel, Schittenhelmstrasse 12, 24105, Kiel, Germany.
authors.forename: Mark
authors.initials: M
authors.lastname: Luedde
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D002097:C-Reactive Protein / Q000378:metabolism; D002116:Calcitonin / Q000378:metabolism; D016022:Case-Control Studies; D016638:Critical Illness / Q000401:mortality*; D000074049:Cytokine TWEAK; D005260:Female; D006801:Humans; D007249:Inflammation / Q000097:blood / Q000378:metabolism / Q000401:mortality / Q000473:pathology; D007362:Intensive Care Units; D015850:Interleukin-6 / Q000378:metabolism; D008024:Ligands; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D018124:Receptors, Tumor Necrosis Factor / Q000378:metabolism; D018805:Sepsis / Q000097:blood* / Q000378:metabolism / Q000401:mortality* / Q000473:pathology; D012720:Severity of Illness Index; D048069:Tumor Necrosis Factors / Q000097:blood*; D055815:Young Adult
chemical_list: D015415:Biomarkers; D000074049:Cytokine TWEAK; D015850:Interleukin-6; D008024:Ligands; D018124:Receptors, Tumor Necrosis Factor; C109743:TNFSF12 protein, human; C478967:TNFSF18 protein, human; D048069:Tumor Necrosis Factors; D002116:Calcitonin; D002097:C-Reactive Protein