Red blood cell transfusion-induced inflammation: myth or reality

Red blood cells (RBCs) destined for transfusion can be refrigerator stored for up to 42 days prior to transfusion. Our studies in mice and dogs suggest that transfusion of older, stored RBCs, but not fresh RBCs, produce acute elevations in circulating pro-inflammatory cytokine levels. Although our study in healthy adult human volunteers failed to demonstrate a pro-inflammatory cytokine response following transfusion of RBCs stored for 40-42 days, a recent study in preterm infants suggests that RBC transfusions are associated with a pro-inflammatory response. Thus, whether RBC transfusions, particularly of older, stored RBCs, result in a pro-inflammatory cytokine response, is still an unresolved issue. Animal studies suggest this to be true, yet human studies have yet to demonstrate definitively that such an inflammatory response occurs. Potential explanations for this include differences between human and animal biology, the dose of RBCs transfused, and baseline differences in levels of inflammation. This review will summarize the currently available evidence and approaches to resolving whether transfusions of older, stored RBCs are associated with inflammation in recipients.