Fenny Chong1, Kelly M Rooks1, Robert L Flower1, Melinda M Dean1,2. 1. Research and Development, Clinical Services and Research, Australian Red Cross Lifeblood, Brisbane, Australia. 2. School of Health and Sport Sciences, University of the Sunshine Coast Moreton Bay, Petrie, Australia.
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)-1β. We assessed whether PRBC supernatants (SN) modulated IL-1β 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-1β driven inflammation. IL-1β 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-1β production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1β and caspase-1 production. PRBC-SN augmented LPS-driven IL-1β and caspase-1 production. Recombinant MIF did not modulate IL-1β production in our model. CONCLUSIONS: Soluble mediators in PRBC modulate monocyte IL-1β 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-1β associated immune modulation.
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)-1β. We assessed whether PRBC supernatants (SN) modulated IL-1β 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-1β driven inflammation. IL-1β 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-1β production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1β and caspase-1 production. PRBC-SN augmented LPS-driven IL-1β and caspase-1 production. Recombinant MIF did not modulate IL-1β production in our model. CONCLUSIONS: Soluble mediators in PRBC modulate monocyte IL-1β 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-1β associated immune modulation.