Recipient cytokine and lipid receptors engaged by residual soluble mediators in the blood product

The term "Recipient cytokine and lipid receptors engaged by residual soluble mediators in the blood product" refers to a heterogeneous group of cell-surface proteins on a transfusion recipient's cells—most notably neutrophils and vascular endothelial cells—that respond to pro-inflammatory substances accumulated during blood component storage (Silliman et al., 2005, Blood). These "residual soluble mediators," often collectively termed the "storage lesion," include cytokines such as Interleukin-1 (IL-1), Interleukin-6 (IL-6), and Interleukin-8 (IL-8), as well as bioactive lipids such as lysophosphatidylcholines (Lyso-PCs) and soluble CD40 ligand (sCD40L) (Zimring, 2013, Transfusion). Upon transfusion, these substances bind to their cognate receptors, such as the IL-6 receptor, CXCR1/2, and the Platelet-Activating Factor (PAF) receptor, triggering intracellular signaling cascades that lead to cellular activation and the release of reactive oxygen species. This interaction is a critical component of the "two-hit" hypothesis for Transfusion-Related Acute Lung Injury (TRALI), where the mediators act as a second stimulus to primed neutrophils in the lung vasculature (Semple et al., 2019, Blood). While this collective term does not describe a single drug target, individual receptors within this pathway are targets for anti-inflammatory therapies like tocilizumab or anakinra in severe inflammatory states. Clinical strategies to mitigate these interactions primarily involve leukoreduction and the use of fresher blood products to limit mediator accumulation (Middleton et al., 2021, Frontiers in Immunology).

Other names

Transfusion-related soluble mediator receptorsStorage lesion-associated receptorsMediators of transfusion-related acute lung injury (TRALI)Bioactive lipid and cytokine receptors in transfusion reactions

Antagonism of specific cytokine or lipid receptors to prevent or mitigate transfusion-related inflammatory responses.