The potential of inflammatory responses to contribute to the development of transfusion-related acute lung injury (TRALI)

Transfusion-related acute lung injury (TRALI) is a significant cause of post-transfusion morbidity and mortality. TRALI develops via a two-insult mechanism: the first insult being the patient's underlying morbidity, and the second insult being transfusion-related. Biological response modifiers (BRMs) that accumulate during blood product storage and anti-leucocyte antibodies are considered causative. Recruitment and activation of neutrophils and monocytes is implicated in TRALI; however, the precise mechanisms remain uncertain. An in vitro transfusion model was developed in which blood from healthy volunteers, incubated with or without lipopolysaccharide (LPS; first insult), was exposed to either a BRM (soluble CD40 ligand (sCD40L), 5-hydroxyeicosatetraenoic acid (HETE), 12-HETE, 15-HETE or interleukin (IL)-8) or an antibody (antibody targeting human leucocyte antigen (HLA) class II). Cytometric bead array, intracellular staining and flow cytometry were used to investigate overall, neutrophil-specific and monocyte-specific inflammatory responses (i.e. changes in concentration or expression of a panel of chemokines and cytokines). Without LPS, inflammatory responses were suppressed following exposure to BRMs or anti-HLA-II, suggesting that less ill patients may have an increased risk of infection following transfusion of these factors. In contrast, in an induced inflammatory state (i.e. with LPS), exposure to anti-HLA-II, IL-8, 12-HETE or 15-HETE resulted in pro-inflammatory changes, suggesting that the transfusion of these factors may contribute to TRALI development in severely ill patients. This study modelled how transfusion-related inflammation may contribute to the development of TRALI. This improved understanding may contribute to the identification of strategies to reduce the risk of TRALI and improve blood transfusion safety