Soluble mediators in packed red blood cells augment lipopolysaccharide-induced monocyte interleukin-1ß production.

ABSTRACT

BACKGROUND AND OBJECTIVES: Soluble mediators in packed red-blood-cell (PRBC) units have been hypothesized as a mechanism associated with transfusion-related immune modulation. Soluble mediators including damage-associated molecular patterns (DAMPs) are known to activate inflammasomes. Inflammasome complexes maturate caspase-1 and interleukin (IL)-1ß. We assessed whether PRBC supernatants (SN) modulated IL-1ß driven inflammation and whether macrophage migration inhibitory factor (MIF) was a contributing factor. MATERIALS AND METHODS: Isolated monocytes were incubated with PRBC-SN in an in vitro transfusion model. Lipopolysaccharide (LPS) was added in parallel to model a bacterial infection. Separately, recombinant MIF was used in the model to assess its role in IL-1ß driven inflammation. IL-1ß and caspase-1 were quantified in the PRBC-SN and culture SN from the in vitro model. RESULTS: PRBC-SN alone did not induce IL-1ß production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1ß and caspase-1 production. PRBC-SN augmented LPS-driven IL-1ß and caspase-1 production. Recombinant MIF did not modulate IL-1ß production in our model. CONCLUSIONS: Soluble mediators in PRBC modulate monocyte IL-1ß inflammation, which may be a contributing factor to adverse effects of transfusion associated with poor patient outcomes. While MIF was present in PRBC-SN, we found no evidence that MIF was responsible for IL-1ß associated immune modulation.