title: Circulating levels of the shed scavenger receptor sCD163 and association with outcome of critically ill patients.
abstract: OBJECTIVE
  CD163, a scavenger receptor for haptoglobin-hemoglobin complexes, is almost exclusively expressed by monocytes and macrophages and is shedded (as sCD163) by inflammatory stimuli. Thus, high serum levels of sCD163 predicted mortality in certain inflammatory diseases. We investigated baseline levels, time course of sCD163 levels and CD163 gene expression in relation to mortality and clinical complications in a large heterogeneous cohort of critically ill patients.
  
  
  METHODS
  In this pre-planned secondary analysis of two randomized clinical studies, critically ill patients (n = 1657) were randomized to "conventional" (insulin administered only for blood glucose levels above 215 mg/dL) or "intensive" insulin therapy (glycemia maintained at 80-110 mg/dL) and compared with healthy controls (n = 112).
  
  
  RESULTS
  Upon admission, critically ill patients had 1.6-fold higher sCD163 levels than controls (P < 0.0001). Long-stay patients (ICU stay >5 days), non-survivors and patients who developed liver dysfunction or kidney injury had higher baseline sCD163 levels. In multivariable analyses, elevated baseline sCD163 levels were independently associated with ICU mortality, liver dysfunction, and time to discharge from ICU and hospital. sCD163 further increased during ICU stay in patients who developed organ dysfunction and in non-survivors. Avoiding hyperglycemia with insulin slightly reduced circulating sCD163 levels. Hepatic CD163 gene expression in patients was higher than in controls (P = 0.002) and correlated positively with sCD163 levels (P = 0.345, P < 0.0001).
  
  
  CONCLUSIONS
  This study hallmarks the association of elevated sCD163 with organ dysfunction and adverse outcome of critical illness and may point to the liver as a potential source.
authors.affiliation: Clinical Department and Laboratory of Intensive Care Medicine, Division Cellular and Molecular Medicine, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.
authors.forename: Catherine
authors.initials: C
authors.lastname: Ingels
authors.forename: Holger J
authors.initials: HJ
authors.lastname: Møller
authors.forename: Troels K
authors.initials: TK
authors.lastname: Hansen
authors.forename: Pieter J
authors.initials: PJ
authors.lastname: Wouters
authors.forename: Ilse
authors.initials: I
authors.lastname: Vanhorebeek
authors.forename: Greet
authors.initials: G
authors.lastname: Van den Berghe
mesh_terms: D000368:Aged; D015703:Antigens, CD / Q000097:blood* / Q000235:genetics; D015214:Antigens, Differentiation, Myelomonocytic / Q000097:blood* / Q000235:genetics; D015897:Comorbidity; D016638:Critical Illness / Q000453:epidemiology* / Q000628:therapy; D005260:Female; D015870:Gene Expression; D017052:Hospital Mortality; D006801:Humans; D007328:Insulin / Q000627:therapeutic use; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D012372:ROC Curve; D011956:Receptors, Cell Surface / Q000097:blood* / Q000235:genetics; D000098902:CD163 Antigen
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000098902:CD163 Antigen; D007328:Insulin; D011956:Receptors, Cell Surface