Background and Aim:

Immune modulation is reported to occur after blood transfusion however, the contributing mechanisms are largely unknown. During routine storage, biological response modifiers (BRMs) accumulate in packed red blood cells (PRBC). These BRMs include a range of cytokines, chemokines and soluble mediators that regulate leucocyte function and recruitment. We investigated BRM levels throughout routine PRBC storage (2-6°C, 42 days). We also assessed whether variation in BRM levels impacted dendritic cell (DC) responses in an in vitro model of transfusion.

Methods:

PRBC units (n=200) were sampled fortnightly and potential BRMs (ICAM-1, VCAM-1, E-selectin, P-selectin, RANTES, sCD40L, Angiogenin, Eotaxin, IP-10, IL-1α, IL-8, IL-9) quantified in PRBC supernatants using cytometric bead array. PRBC units were then chosen based on BRM level (“high” (top 10) and “low” (bottom 10)). Using an in vitro model of transfusion with concurrent infection (+LPS), DC inflammatory mediators (IL-6, IL-8, IL-10, IL-12, IL-1α, TNF-α, MIP-1α, MIP-1β, MCP-1, IP-10) were assessed following exposure to media (control) or supernatants from PRBC units with “high” or “low” BRMs. DC responses were calculated as a ratio to LPS only, and then responses to “high” and “low” BRM were compared (unpaired t-test, P<0.05). 

Results:

Inter-unit variation in levels of BRMs in PRBC was observed with clear subpopulations of PRBC units with high- or low-BRMs. In the transfusion concurrent infection model we found differential modulation of DC phenotype depending BRM levels in PRBC. High BRM PRBC resulted in significant suppression of DC production of IL-1α, TNF-α, MIP-1α and MIP-1β compared to low BRM PRBC.

Conclusions:

PRBC containing higher levels of BRMs attenuated the LPS-induced DC inflammatory response more than those with low BRM levels. Patients’ receiving PRBC containing high BRMs may be at greater risk of increased severity and vulnerability to infection, potentially leading to longer hospital stays and higher mortality.