Transfusion of stored blood impairs host defenses against Gram-negative pathogens in mice.
BACKGROUND
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.


METHODS
To assess the effects of increased iron availability on susceptibility to infection, we infected mice with model Gram-negative intracellular or extracellular pathogens (Salmonella typhimurium or Escherichia coli, respectively), accompanied by RBC transfusion, iron dextran administration, or malarial coinfection.


RESULTS
In our mouse models, transfusion of older RBCs exacerbates infection with both Gram-negative pathogens. Although iron dextran exacerbates E. coli infection to a similar extent as transfusion of corresponding amounts of iron, higher iron doses are required to produce comparable effects with S. typhimurium. Coinfection of mice with Plasmodium yoelii and S. typhimurium produces overwhelming Salmonella sepsis. Finally, treating mice with antibiotics abrogates the enhancing effect on E. coli infection of both older RBC transfusion and iron dextran administration.


CONCLUSIONS
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 E. coli. Iron delivery to macrophages may be an underappreciated mechanism mediating, at least some, adverse effects of RBC transfusions.
Institute of Comparative Medicine, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York; Department of Pathology and Cell Biology, Columbia University Medical Center-New York Presbyterian Hospital, New York, New York.
Kevin
K
Prestia
Sheila
S
Bandyopadhyay
Andrea
A
Slate
Richard O
RO
Francis
Kevin P
KP
Francis
Steven L
SL
Spitalnik
David A
DA
Fidock
Gary M
GM
Brittenham
Eldad A
EA
Hod
D000818:Animals; D001793:Blood Preservation / Q000009:adverse effects*; D004195:Disease Models, Animal; D017707:Erythrocyte Transfusion; D004926:Escherichia coli / Q000276:immunology* / Q000378:metabolism; D004927:Escherichia coli Infections / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D006461:Hemolysis; D006801:Humans; D007501:Iron / Q000276:immunology* / Q000378:metabolism; D008264:Macrophages / Q000276:immunology / Q000378:metabolism; D008288:Malaria / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D010967:Plasmodium yoelii / Q000276:immunology / Q000378:metabolism; D012480:Salmonella Infections / Q000209:etiology / Q000276:immunology* / Q000378:metabolism; D012486:Salmonella typhimurium / Q000276:immunology* / Q000378:metabolism; D018805:Sepsis / Q000209:etiology / Q000276:immunology* / Q000378:metabolism
D007501:Iron