title: Red blood cell transfusion and immune function in critically ill children: a prospective observational study.
abstract: BACKGROUND
  Our previous in vitro work showed that stored red blood cells (RBCs) increasingly suppress markers of innate immune function with increased storage time. This multicenter prospective observational study tests the hypothesis that a single RBC transfusion in critically ill children is associated with immune suppression as a function of storage time.
  
  
  METHODS
  Blood samples were taken immediately before and 24 (±6) hours after a single RBC transfusion ordered as part of routine care. Innate and adaptive immune function was assessed by ex vivo whole blood stimulation with lipopolysaccharide (LPS) and phytohemagglutinin, respectively. Monocyte HLA-DR expression, regulatory T cells, plasma interleukin (IL)-6, and IL-8 levels were also measured.
  
  
  RESULTS
  Thirty-one transfused critically ill children and eight healthy controls were studied. Critically ill subjects had lower pretransfusion LPS-induced tumor necrosis factor-α production capacity compared to healthy controls, indicating innate immune suppression (p < 0.0002). Those who received RBCs stored for not more than 21 days demonstrated recovery of innate immune function (p = 0.02) and decreased plasma IL-6 levels (p = 0.002) over time compared to children transfused with older blood, who showed persistence of systemic inflammation and innate immune suppression. RBC storage time was not associated with changes in adaptive immune function.
  
  
  CONCLUSIONS
  In this pilot cohort of critically ill children, transfusion with older prestorage leukoreduced RBCs was associated with persistence of innate immune suppression and systemic inflammation. This was not seen with fresher RBCs. RBC transfusion had no short-term association with adaptive immune function. Further studies are warranted to confirm these findings in a larger cohort of patients.
authors.affiliation: Pediatric Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.|The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Jennifer A
authors.initials: JA
authors.lastname: Muszynski
authors.affiliation: Pediatrics, Division of Critical Care Medicine, Washington University, St Louis, Missouri.
authors.forename: Elfaridah
authors.initials: E
authors.lastname: Frazier
authors.affiliation: Critical Care Medicine, Department of Pediatrics, Akron Children's Hospital, Akron, Ohio.
authors.forename: Ryan
authors.initials: R
authors.lastname: Nofziger
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Jyotsna
authors.initials: J
authors.lastname: Nateri
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Lisa
authors.initials: L
authors.lastname: Hanson-Huber
authors.affiliation: The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Lisa
authors.initials: L
authors.lastname: Steele
authors.affiliation: Pathology, Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Kathleen
authors.initials: K
authors.lastname: Nicol
authors.affiliation: Pediatrics, Division of Critical Care Medicine, Washington University, St Louis, Missouri.
authors.forename: Philip C
authors.initials: PC
authors.lastname: Spinella
authors.affiliation: Pediatric Critical Care Medicine, Department of Pediatrics, Nationwide Children's Hospital, Columbus, Ohio.|The Research Institute at Nationwide Children's Hospital, Columbus, Ohio.
authors.forename: Mark W
authors.initials: MW
authors.lastname: Hall
mesh_terms: D056704:Adaptive Immunity; D001793:Blood Preservation; D002648:Child; D002675:Child, Preschool; D016638:Critical Illness / Q000628:therapy*; D004905:Erythrocyte Aging; D017707:Erythrocyte Transfusion; D005260:Female; D006801:Humans; D007113:Immunity, Innate; D007223:Infant; D007249:Inflammation; D007371:Interferon-gamma / Q000096:biosynthesis / Q000097:blood; D007378:Interleukins / Q000096:biosynthesis / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008213:Lymphocyte Activation / Q000187:drug effects; D008297:Male; D010835:Phytohemagglutinins / Q000494:pharmacology; D010865:Pilot Projects; D011446:Prospective Studies; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis / Q000096:biosynthesis
chemical_list: D007378:Interleukins; D008070:Lipopolysaccharides; D010835:Phytohemagglutinins; D014409:Tumor Necrosis Factor-alpha; D007371:Interferon-gamma