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Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production
Journal article   Peer reviewed

Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β production

Fenny Chong, Kelly M Rooks, Robert L Flower and Melinda M Dean
Vox Sanguinis, Vol.115(7), pp.562-569
2020
url
https://doi.org/10.1111/vox.12915View
Published Version

Abstract

immunohaematology cytokine blood safety
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 ILL‐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.

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