Anna L Peters1,2, Maike E van Hezel1,2,3, Robert B Klanderman1,2, Anita M Tuip-de Boer1,2, W Joost Wiersinga4, Anne H van der Spek5, Robin van Bruggen3, Dirk de Korte3,6, Nicole P Juffermans1,2, Alexander P J Vlaar1,2. 1. Laboratory of Experimental Intensive Care and Anesthesia, Sanquin Blood Supply, Amsterdam, the Netherlands. 2. Department of Intensive Care, Sanquin Blood Supply, Amsterdam, the Netherlands. 3. Department of Blood Cell Research, Sanquin Research, Amsterdam, the Netherlands. 4. Department of Medicine, Division of Infectious Diseases, Sanquin Blood Supply, Amsterdam, the Netherlands. 5. Department of Endocrinology and Metabolism, Academic Medical Center, Amsterdam, the Netherlands. 6. Department of Product and Process Development, Sanquin Blood Supply, Amsterdam, the Netherlands.
Abstract
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.
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 humanendotoxemia, 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.
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Authors: Tom A P Driedonks; Sanne Mol; Sanne de Bruin; Anna-Linda Peters; Xiaogang Zhang; Marthe F S Lindenbergh; Boukje M Beuger; Anne-Marieke D van Stalborch; Thom Spaan; Esther C de Jong; Erhard van der Vries; Coert Margadant; Robin van Bruggen; Alexander P J Vlaar; Tom Groot Kormelink; Esther N M Nolte-'t Hoen Journal: J Extracell Vesicles Date: 2020-05-26
Authors: Maike E van Hezel; Margit Boshuizen; Anna L Peters; M Straat; Alexander P Vlaar; Angelique M E Spoelstra-de Man; Michael W T Tanck; Anton T J Tool; Boukje M Beuger; Taco W Kuijpers; Nicole P Juffermans; Robin van Bruggen Journal: Transfusion Date: 2019-12-05 Impact factor: 3.157