Transfusion of stored blood impairs host defenses against Gram‐negative pathogens in mice. Issue 11 (19th May 2014)

• Record Type: Journal Article
• Authors: Prestia, Kevin; Bandyopadhyay, Sheila; Slate, Andrea; Francis, Richard O.; Francis, Kevin P.; Spitalnik, Steven L.; Fidock, David A.; Brittenham, Gary M.; Hod, Eldad A.
• Is Part Of: Transfusion. Volume 54:Issue 11(2014)
• Page Start: 2842
• Page End: 2851
• Publication Date: 2014-05-19
• Subjects: Hematology -- Periodicals; Blood -- Transfusion -- Periodicals; Blood Group Antigens -- Periodicals; Blood Preservation -- Periodicals; Blood Transfusion -- Periodicals; 615
• DOI: 10.1111/trf.12712
• Languages: English
• ISSNs: 0041-1132

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <sec id="trf12712-sec-0001" sec-type="section"> <title>Background</title> <p>Although human red blood cell (RBC) units may be refrigerator stored for up to 42 days, transfusion of older RBCs acutely delivers a large bolus of iron to mononuclear phagocytes. Similarly, iron dextran circulates in plasma for hours to days and is progressively cleared by mononuclear phagocytes, which return iron to plasma. Finally, malaria infection continuously delivers iron to macrophages by intra‐ and extravascular hemolysis. Studies suggest that iron administration increases infectious risk.</p> </sec> <sec id="trf12712-sec-0002" sec-type="section"> <title>Study Design and Methods</title> <p>To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram‐negative intracellular or extracellular pathogens (<italic>Salmonella typhimurium</italic> or <italic>Escherichia coli</italic>, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection.</p> </sec> <sec id="trf12712-sec-0003" sec-type="section"> <title>Results</title> <p>In our mouse models, transfusion of older RBCs exacerbates infection with both Gram‐negative pathogens. Although iron dextran exacerbates <italic>E. coli</italic> infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with <italic>S. typhimurium</italic>. Coinfection of mice with <italic>Plasmodium yoelii</italic> and <italic>S. typhimurium</italic> produces overwhelming <italic>Salmonella</italic> sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on <italic>E. coli</italic> infection of both older RBC transfusion and iron dextran administration.</p> </sec> <sec id="trf12712-sec-0004" sec-type="section"> <title>Conclusions</title> <p>Transfusion of older RBCs exacerbates Gram‐negative infection to a similar extent as malaria coinfection or iron dextran administration. Appropriate antibiotic therapy abrogates the effect of older RBC transfusions on infection with <italic>E. coli.</italic> Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions.</p> </sec> </abstract>