Table 1.

TREM-1 pathway inhibitory strategies.

Treatment	Sepsis Model	Cell/Animal	Effect	Ref.
sTREM-1	LPS	Macrophages	↓ mRNA of inflammatory cytokines	(69)
	S. suis intraperitoneal	Mice	↓ serum TNF-α, IL-1β, ↓ acute lung injury, ↑ survival (when given with antibiotics)	(70)
TREM-1 Fc fusion protein	LPS	Monocytes	↓ release TNF-α, IL-1β	(8)
	P. aeruginosa	Macrophages	↓ release TNF-α, IL-1β, MCP-1	(71)
	S. pyogenes	Neutrophils	↓ release IL-6, TNF-α	(72)
	LPS intraperitoneal	Mice	↓ serum TNF-α, IL-1β, ↓ recruitment of peritoneal macrophages and neutrophils, ↑ survival	(8)
	CLP	Mice	↑ survival	(8)
	E. coli intraperitoneal	Mice	↑ survival	(8)
	S. pyogenes intravenous	Mice	↓ serum IL-6, TNF-α, ↑ survival	(72)
	P. aeruginosa intraperitoneal	Mice	↓ serum IL-1β, TNF-α, MCP-1, ↑ survival	(71)
LP17	LPS	Monocytes	↓ release TNF-α, IL-1β	(73)
	E. coli	Neonatal leukocytes	↓ release TNF-α, IL-6, IL-8	(74)
	LPS intraperitoneal	Mice	↑ survival	(35)
	CLP	Mice	↓ serum TNF-α, IL-1β, ↑ survival	(73)
	S. pyogenes intravenous	Mice	↑ survival	(72)
	LPS intraperitoneal	Rats	↑ hemodynamics, ↓ serum TNF-α, IL-1β	(35)
	CLP	Rats	↑ hemodynamics, ↓ TNF-α, IL-1β, IL-6, ↑ survival	(35, 75)
	P. aeruginosa intratracheal	Rats	↓ serum and broncoalveolar lavage TNF-α, IL-1β, IL-6, lactic acidosis, hypoxia, ↑ hemodynamics, ↑ survival	(76)
GF9	LPS	Macrophages	↓ release TNF-α, IL-1β, IL-6	(77)
	LPS intraperitoneal	Mice	↓ serum TNF-α, IL-1β, IL-6, ↑ survival	(77)
SLC-TREM-1	LPS	Endothelium	↓ TREM-1 expression, ↓ MCP-1, IL-8 release	(78)
	CLP	Mice	↑ survival	(78)
M3	LPS intraperitoneal	Mice	↓ serum TNF-α, IL-6, ↑ survival	(41)
	CLP	Mice	↓ serum AST, ALT, TNF-α, IL-6, ↓ acute lung injury, ↑ survival	(41)
	Cecal Slurry	Neonatal Mice	↓ serum TNF-α, IL-1β, IL-6, INFγ, ↓ cardiac and pulmonary IL-1β, IL-6, ↓ cardiac dysfunction, ↑ survival	(79)
N1	LPS	Mononuclear Cells/Monocytes	↓ mRNA TNF-α, IFNγ, IL-1β, and IL-6	(80)
	LPS intrabronchial	Mice	↓ serum INFγ, IL-4, ↓ lung damage	(80)
LR17/LR12	LPS	Granulocyte	↓ mRNA and protein TNF-α, IL-8, IL-10, ↓ ROS production	(23)
	LPS	Monocytes	↓ release TNF-α	(23)
	LPS intraperitoneal	Mice	↓ serum TNF-α, IL-6, IL-10, ↑ survival	(23)
	CLP	Mice	↓ cytokines in serum, peritoneal and bronchoalveolar fluid, liver, lung, ↓ acute lung injury, ↓ bacteria in spleen, blood, ↓ TREM-1 expression, ↑ survival	(23, 57)
	Cecal Slurry	Pigs	↑ cardiac function, ↓ coagulopathy, ↓ failure of lungs, liver, kidney, ↑survival	(68)
	LPS intravenous	Monkeys	↑ hemodynamics, ↓ serum cytokines	(81)
Nangibotide	Sepsis	Humans	↓ systemic IL-6, ↓ SOFA scores, minimal side effects	(82, 83)

↓- decreased; ↑- increased.