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Transfusion of 35‐day‐stored red blood cells does not alter lipopolysaccharide tolerance during human endotoxemia
Author(s) -
Peters Anna L.,
van Hezel Maike E.,
Klanderman Robert B.,
Tuipde Boer Anita M.,
Wiersinga W. Joost,
van der Spek Anne H.,
van Bruggen Robin,
de Korte Dirk,
Juffermans Nicole P.,
Vlaar Alexander P.J.
Publication year - 2017
Publication title -
transfusion
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.045
H-Index - 132
eISSN - 1537-2995
pISSN - 0041-1132
DOI - 10.1111/trf.14087
Subject(s) - ex vivo , cytokine , lipopolysaccharide , in vivo , whole blood , medicine , proinflammatory cytokine , stimulation , immunology , red blood cell , pharmacology , biology , inflammation , microbiology and biotechnology
BACKGROUND 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. STUDY DESIGN AND METHODS 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. RESULTS 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. CONCLUSION 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.