title: Transfusion of 35-day-stored red blood cells does not alter lipopolysaccharide tolerance during human endotoxemia.
abstract: Transfusion-related immunomodulation (TRIM) encompasses immunosuppressive and proinflammatory effects induced by red blood cell (RBC) transfusion. Changes that occur during storage in the RBC product have been hypothesized to underlie TRIM, mediated by tolerance of toll-like receptors (TLR). We investigated whether transfusion of 35-day-stored autologous RBCs alters cytokine production in response to stimulation with lipopolysaccharide (LPS) or lipotheic acid (LTA), in a clinically relevant model of endotoxemia.
  
  
  
  Eighteen volunteers received 2 ng/kg LPS intravenously, followed by normal saline or 2- or 35-day-stored autologous RBC transfusion. Before LPS, before transfusion, and 6 hours after transfusion blood was collected to measure cytokine gene expression. Whole blood was used for ex vivo stimulation with LPS and LTA, after which cytokine levels were measured with enzyme-linked immunosorbent assay.
  
  
  
  In vivo LPS induced a biphasic response in cytokine mRNA with peak values 2 hours after LPS infusion. Storage time of RBC transfusion did not influence cytokine mRNA levels. In vivo infusion of LPS resulted in tolerance for ex vivo stimulation with LPS and LTA. However, transfusion of either fresh or stored RBCs did not further affect the capacity to produce cytokines after ex vivo stimulation.
  
  
  
  In a clinically relevant model of human endotoxemia, autologous transfusion of 35-day-stored RBCs does not influence cytokine mRNA levels nor does it change the capacity of white blood cells in whole blood to produce cytokines after ex vivo stimulation with LPS or LTA.
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Anna L
authors.initials: AL
authors.lastname: Peters
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands.
authors.forename: Maike E
authors.initials: ME
authors.lastname: van Hezel
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Robert B
authors.initials: RB
authors.lastname: Klanderman
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Anita M
authors.initials: AM
authors.lastname: Tuip-de Boer
authors.affiliation: Department of Medicine, Division of Infectious Diseases, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: W Joost
authors.initials: WJ
authors.lastname: Wiersinga
authors.affiliation: Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, the Netherlands.
authors.forename: Anne H
authors.initials: AH
authors.lastname: van der Spek
authors.affiliation: Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands.
authors.forename: Robin
authors.initials: R
authors.lastname: van Bruggen
authors.affiliation: Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands.|Department of Product and Process Development, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Dirk
authors.initials: D
authors.lastname: de Korte
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Nicole P
authors.initials: NP
authors.lastname: Juffermans
authors.affiliation: Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands.|Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands.
authors.forename: Alexander P J
authors.initials: APJ
authors.lastname: Vlaar
mesh_terms: D000293:Adolescent; D000328:Adult; D001793:Blood Preservation; D019446:Endotoxemia / Q000628:therapy*; D017707:Erythrocyte Transfusion; D004912:Erythrocytes / Q000187:drug effects / Q000502:physiology; D005260:Female; D064368:Healthy Volunteers; D006801:Humans; D008070:Lipopolysaccharides / Q000633:toxicity*; D008297:Male; D055815:Young Adult
chemical_list: D008070:Lipopolysaccharides