TABLE 1.

Summary of therapeutic strategy targeting neutrophils.

Target	Strategies	Outcomes	References
Neutrophil	Anti–Gr-1	Reduces remote lung and liver injury in a mice CLP model	Wickel et al. (1997)
	Leucofiltration	Improves organ function in human patients with severe sepsis	Lewis et al. (2013)
	GM-CSF	Drives the maturation and proliferation of neutrophils; Phase III study ongoing	NCT02361528; Meisel et al. (2009), Hall et al. (2011)
	G-CSF	No improvement in clinical trial study	Root et al. (2003)
	Inhibition of Wip1	Drives the maturation of neutrophils and enhances their antimicrobial function	Shen et al. (2017b)
	Anti–PD-L1	Restores T-cell function in the mice model	Zhang et al. (2010)
NETs	DNase I	Effective when combined with antibiotics to improve the outcome	Czaikoski et al. (2016)
	Cl-amidine	Prevents NETs formation and improves survival in a mice CLP model	Biron et al. (2017)
	Anti-citrullinated histone 3	Reduces NETs and improves survival in a mice CLP model	Li et al. (2014)
	Anti–TREM-1	Prevents NETosis and associated endothelial dysfunction in a mice LPS model	Murao et al. (2020), Boufenzer et al. (2021)
Histone	Anti-histone	Improves the outcome in the LPS, TNF, and CLP mice models	Meara et al. (2020)
	Activated protein C	Failed in the clinic	Marti-Carvajal et al. (2012)
Platelet	Acetylsalicylic acid	Decreases intravascular NETosis and tissue injury	Caudrillier et al. (2012)
	Aspirin	Ongoing clinical trial	Eisen et al. (2017)
	Anti-P2Y12	Prevents NETosis and improves the survival in mice CLP model	Liverani et al. (2016), Mansour et al. (2020)
	Antiplatelet factor 4	Stabilizes NETs and prevents the release of antibacterial compounds in mice model	Gollomp et al. (2020)