Soluble mediators in packed red blood cells augment lipopolysaccharide‐induced monocyte interleukin‐1β 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)-1b. We assessed whether PRBC supernatants (SN) modulated IL-1b 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-1b driven inflammation. IL-1b 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-1b production from monocytes. However, PRBC-SN alone increased caspase-1 production. LPS alone induced both IL-1b and caspase-1 production. PRBC-SN augmented LPS-driven IL-1b and caspase-1 production. Recombinant MIF did not modulate IL-1b production in our model. Conclusions Soluble mediators in PRBC modulate monocyte IL-1b 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-1b associated immune modulation.

Damaged Mesenchymal Cells Dampen the Inflammatory Response of Macrophages and the Formation of Osteoclasts

“…However, we tried to simulate a mechanical injury by sonication and freeze/thawing of ST2 cells, while others provoked osteocyte necrosis by the lack of nutrition [ 11 , 13 ]. Moreover, in contrast to our findings are the observations based on soluble mediators in erythrocytes that enhanced monocyte IL1β inflammation [ 24 ], and in general, signals released by damaged cells are overall proinflammatory in nature [ 16 , 17 ]. Thus, the consensus is that soluble mediators that are naturally released exert a pro-inflammatory activity on macrophages and support the process of osteoclastogenesis.…”

“…However, we tried to simulate a mechanical injury by sonication and freeze/thawing of ST2 cells, while others provoked osteocyte necrosis by the lack of nutrition [11,13]. Moreover, in contrast to our findings are the observations based on soluble mediators in erythrocytes that enhanced monocyte IL1β inflammation [24], and in general, signals released by damaged…”