Table 2.

Summary of innovative treatments undergoing TRALI.

Disease	Targeting	Strategy	Delivery Route	Treatment Regiment	Results/ Outcomes	Proposed mechanism of action	Type of study	References
TRALI	Supportive care	Oxygen inhalation	Not mentioned	Not mentioned	Relieving respiratory distress	Maintaining hemodynamics	Review	Semple et al. (13), 2019
							Review	Kuldanek et al. (126), 2019
		Ventilation	Invasive	Not mentioned			Review	Kuldanek et al. (126), 2019
			Noninvasive	Not mentioned
		Extra-corporeal membrane oxygenation	Intravenous catheterization	Not mentioned			Review	Kuldanek et al. (126), 2019
				Lasting 15 h after the operation			Case reports	Honda et al. (131), 2015
	Serum proinflammatory, anti-inflammatory markers levles, and oxidative stress	Ascorbic acid	I.V.	2.5 gm/6 h, 96 h	Better 7-days survival	Reduced most proinflammatory markers levels and oxidative stress; elevated anti-inflammatory marker	Clinical trial	Kassem et al. (132), 2022
	Gut glora	Broad spectrum;(vancomycin, ampicillin, neomycin, and metronidazole)	Oral	1 mg/mL, every 48 hours for 1 week	Preventing murine TRALI	Decreasing plasma MIP-2 levels and pulmonary PMN recruitment	Preclinical study	Kapur R et al. (24), 2018
Antibody-dependent TRALI	NETs	Aspirin	I.P.	100 μg/g, 30 min prior to LPS priming and again 2 h prior to MHC-I mAb challenge.	Alleviating lung injury	Decreasing NET formation and NET-associated platelets sequestration	Preclinical study	Caudrillier et al. (78), 2012
		DNase1	I.V.	10 mg/kg, at the same time of H2Kd mAb injection; 5 minutes after H2Kd mAb injection	Alleviating lung injury	Decreasing NET formation and NET-associated platelets sequestration	Preclinical study	Caudrillier et al. (78), 2012
		DNase1	Intranasal	50 μg/mouse, 10 min before or 90 min after H2Kd antibody injection.	Improving arterial oxygen saturation	Disrupting NET accumulation	Preclinical study	Thomas et al. (81), 2012
		Disulfiram	I.P.	50 mg/kg, 24 h and 3 h before H2Kd antibody injection.	Improving survival	Blockade of NET formation	Preclinical study	Adrover et al. (91), 2022
		MSI-1436	I.P.	10 mg/kg, 2 h before TRALI induction	Preventing murine TRALI and improving survival	Limiting NET production	Preclinical study	Song et al. (46), 2022
	ROS	IVIg	I.P.	2 g/kg, 18 h before 34-1-2S injection; 1 g/kg dose of IVIg 3 min post 34-1-2S injection	Preventing TRALI as well as reducing lung injury	Inhibiting PMN derived ROS production	Preclinical study	Semple et al. (97), 2012
	PMNs	MSI-1436	I.P.	Optimal dose of 10 mg/kg, 2 h before 34-1-2S injection.	Preventing murine TRALI and improving survival	Promoting PMN aging	Preclinical study	Song et al. (46), 2022
		Dasatinib	Oral	Not mentioned	Alleviating lung injury	Inhibited PMN activation	Preclinical study	Le et al. (49), 2022
	ECs	IL-35	I.V.	100 μg/kg, once a day for 2 days before the TRALI model, and the model was generated on the third day, with a third injection before 34-1-2S injection.	Preventing TRALI	Inhibition of endothelial activation	Preclinical study	Qiao et al. (133), 2020
	Macrophage	anti-OPN antibody	I.V.	2.25 mg/kg, injected with TRALI induction antibodies	Preventing TRALI onset	Blocking OPN derived from macrophages	Preclinical study	Kapur et al. (26), 2019
		AAT	Exogenous gene delivery; hydrodynamic injection	A mixture of a pattB-CMV-AAT and a mouse codon-optimized PhiC31o vector was codelivered to hepatocytes by hydrodynamic injection	Alleviating lung injury	Suppressing AMs polarization toward the proinflammatory M1 phenotype	Preclinical study	Wang et al. (74), 2020
	Platelets	Sarpogrelate	I.V.	1 mg/kg,5min before 34-1-2S injection; injection after TRALI induction	Abolishing lung edema	Blockade of platelet FcγRIIA/CD32A activation mediated serotonin secretion	Preclinical study	El Mdawar et al. (84), 2021
		Tirofiban	I.V.	2 μg/g, 30min before 34-1-2S injection	Decreasing lung injury	Suppressing platelet activation and targeting pulmonary coagulation-fibrinolytic disorders	Preclinical study	Yuan et al. (134), 2023
	Anti-inflammatory cytokine	IL-10	I.V.	45 mg/kg, together with the TRALI induction antibodies or 15 min after injection of TRALI induction antibodies	Protecting and rescuing murine TRALI	Removal of a major anti-inflammatory brake.	Preclinical study	Kapur et al. (32), 2017
	Treg	IL-2/IL-2c	I.P.	IL-2 5μg/kg or IL-2c (1 mg of recombinant murine IL-2 and 10 mg of mouse IL-2 antibody) administered to mice for 5 consecutive days before TRALI model induction	Preventing murine TRALI	Activation of Treg-IL-10 axis	Preclinical study	He et al. (135), 2019

TRALI, transfusion-related acute lung injury; h, hour; I.V., intravenous injection; I.P., intraperitoneal injection; min, minute; MIP-2, macrophage inflammatory protein-2; NETs, neutrophil extracellular traps; ROS, reactive oxygen species; mAb, monoclonal antibody; IVIg, intravenous immunoglobulin; PMNs, polymorphonuclear neutrophils; ECs, endothelial cells; IL, interleukin; OPN, osteopontin; α1-antitrypsin, AAT; AM, alveolar macrophage; FcγR, IgG receptor; IL-2c, anti-IL-2 complexes; Treg, regulatory T cell.