title: Transfusion of cryopreserved human red blood cells into healthy humans is associated with rapid extravascular hemolysis without a proinflammatory cytokine response.
abstract: BACKGROUND
  Transfusion of stored red blood cells (RBCs) can be associated with adverse side effects. Recent studies in mice transfused with stored RBCs showed that a strong proinflammatory cytokine storm was induced due to extravascular hemolysis already at 2 hours after transfusion. Therefore, we here investigated if transfusion of 2 units of cryopreserved autologous RBCs induced a proinflammatory response in healthy human volunteers.
  
  
  METHODS
  Two units of autologous RBCs, cryopreserved for 16 weeks, were transfused into 10 healthy human volunteers. Serum and blood samples taken at 2 hours before and at 2 and 48 hours after transfusion were analyzed for signs of extravascular hemolysis and the presence of proinflammatory cytokines.
  
  
  RESULTS
  At 2 hours after transfusion, transferin-bound serum iron, as well as transferin saturation and total bilirubin, were already significantly increased. These measures all returned back toward that in pretransfusion samples at 48 hours after transfusion. No increases in the production of the proinflammatory cytokines interleukin (IL)-1β, IL-6, IL-8, monocyte chemotactic protein-1, macrophage inflammatory protein-1β, or tumor necrosis factor-α were detected at any time point after transfusion.
  
  
  CONCLUSIONS
  Although a significant level of extravascular hemolysis already occurred at 2 hours after transfusion of cryopreserved RBCs, there were no signs of proinflammatory cytokine production up to 48 hours after transfusion.
authors.affiliation: Department of Integrative Medical Biology, Section for Histology and Cell Biology, Umeå University, Umeå, SE-90187, Sweden.
authors.forename: Andreas
authors.initials: A
authors.lastname: Hult
authors.forename: Christer
authors.initials: C
authors.lastname: Malm
authors.forename: Per-Arne
authors.initials: PA
authors.lastname: Oldenborg
mesh_terms: D000328:Adult; D018932:Chemokine CCL2; D015925:Cryopreservation; D016207:Cytokines / Q000378:metabolism*; D017707:Erythrocyte Transfusion / Q000009:adverse effects*; D004912:Erythrocytes / Q000166:cytology* / Q000378:metabolism*; D006461:Hemolysis / Q000502:physiology*; D006801:Humans; D016753:Interleukin-10 / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism; D016209:Interleukin-8 / Q000378:metabolism; D008297:Male; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D055815:Young Adult
chemical_list: D018932:Chemokine CCL2; D016207:Cytokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10