Transfusion-related acute lung injury (TRALI) is a severe adverse event and a leading cause of transfusion-associated death. Its poor associated prognosis is due, in large part, to the current dearth of effective therapeutic strategies. Hence, an urgent need exists for effective management strategies for the prevention and treatment of associated lung edema. Recently, various preclinical and clinical studies have advanced the current knowledge regarding TRALI pathogenesis. In fact, the application of this knowledge to patient management has successfully decreased TRALI-associated morbidity. This article reviews the most relevant data and recent progress related to TRALI pathogenesis. Based on the existing two-hit theory, a novel three-step pathogenesis model composed of a priming step, pulmonary reaction, and effector phase is postulated to explain the process of TRALI. TRALI pathogenesis stage-specific management strategies based on clinical studies and preclinical models are summarized with an explication of their models of prevention and experimental drugs. The primary aim of this review is to provide useful insights regarding the underlying pathogenesis of TRALI to inform the development of preventive or therapeutic alternatives.
BACKGROUNDTransfusion‐related acute lung injury (TRALI) is an important cause of death associated with transfusion, and no specific clinical treatments are available. Endothelial cells are believed to play an important role in the development of TRALI. This study investigated whether IL‐35, an endothelial stabilizing cytokine could regulate the severity of antibody‐mediated TRALI in vivo.STUDY DESIGN AND METHODSHuman microvascular endothelial cells (HMVECs) were cultured in vitro, rIL‐35(2 μg/mL) was added before HMVECs activation, and HMVECs were fully activated by LPS (0.5 μg/mL). Then cells were collected for flow cytometry analysis. We used a previously established “two‐event” mouse model of TRALI with naive and lipopolysaccharide (LPS)‐injected mice as controls. rIL‐35(100 μg/kg) was injected into the tail vein for 3 consecutive days before the induction of the TRALI model. Samples were collected 2 hours after TRALI induction and tested for lung tissue myeloperoxidase activity, total protein levels, lung tissue histology, endothelial cell activation assay, and cytokine assay.RESULTSIn vitro culture of HMVECs with rIL‐35 verified that rIL‐35 inhibited endothelial cells. In a mouse model, prophylactic administration of rIL‐35 prevented pulmonary edema, increased lung protein levels, and reduced polymorphonuclear neutrophil accumulation in the lung.CONCLUSIONSThis work suggests that antibody‐mediated murine TRALI can be prevented by rIL‐35, and that rIL‐35 appears to work by inhibiting the activation of lung endothelial cells.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.