Impact of alloantigens and storage-associated factors on stimulated cytokine response in an in vitro model of blood transfusion

Background: Transfusion of blood may contribute to immunosuppression in major surgery. The authors assessed the impact of alloantigens and storage on function of peripheral blood mononuclear cells cultured in their physiologic environment. Methods: Blood units (whole blood, packed erythrocytes) were prepared with or without prestorage leukodepletion and stored for 24-26 days. Blood samples were coincubated with allogeneic fresh blood, autologous, or allogeneic stored blood. Endotoxin-stimulated release of tumor necrosis factor-alpha (TNF-alpha) and interleukin 10 (IL-10) was measured after 24 h of culture by enzyme-linked immunosorbent assay. Results: Coincubation with equal amounts of allogeneic fresh blood showed almost no influence on TNF-alpha (-12%, not significant) and IL-10 (+11%, not significant) release. Stored allogeneic whole blood resulted in a significant TNF-alpha depression (-61%) and IL-10 induction (+221%). These effects were diminished but not prevented by prestorage leukodepletion (TNF-alpha -42% IL-10 +110%) and required the presence of soluble factors (TNF-alpha suppression) and cellular components (IL-10 induction). TNF-alpha decrease and IL-10 increase were in the same order of magnitude (-40%, +134% with, -65%, +314% without leukodepletion) after coincubation with autologous; blood. In contrast, allogeneic erythrocytes had only little effects (TNF-alpha -6%, IL10 + 36%) even at this high transfusion equivalent. Conclusion: These data suggest that banked whole blood has an immunosuppressive effect that is largely attributable to storage-dependent factors. These factors are partially removed by prestorage leukodepletion, while the contribution of alloantigens is of minor significance. Immunosuppressive effects are least apparent with leukodepleted erythrocytes, suggesting that the presence of plasma during storage is required for the immunosuppressive effect to develop.