. Author manuscript; available in PMC: 2009 Dec 2.

Published in final edited form as: Nat Rev Immunol. 2008 Oct;8(10):776–787. doi: 10.1038/nri2402

Table 1.

Potential therapeutic targets in sepsis

System	Proposed mechanism	Target	References
Pattern- recognition system	Inhibition of PRRs to dampen the inflammatory response	TLR4 blockade	23

		RAGE blockade	49

Pro-inflammatory mediators	Blockade of central hubs of the inflammatory response to reverse established sepsis	MIF blockade or inhibition of its tautomerase activity	36,37

		HMGB1 blockade	44,50

		IL-17A blockade	52

Complement system	Neutralization of the harmful effects of C5a; formation of the MAC not affected	C5a neutralization	58

		Dual C5AR and C5L2 blockade	29

Coagulation system	Induction of anticoagulant and anti-inflammatory effects	Administration of activated protein C	74

		Selective PAR1 and PAR2 activation	83

Autonomic nervous system	Activation of the cholinergic anti-inflammatory pathway and/or suppression of the adrenergic pro-inflammatory pathway to restore homeostasis	Parasympathetic branch:
		• Pharmacological stimulation of ^α₇nAChR on immune cells	42
		• Vagus-nerve stimulation	104

		Sympathetic branch:
		• Pharmacological modulation of ^α- and β-adrenergic receptor pathways on leukocytes	12, 108

α₇nAChR, α₇-nicotinic acetylcholine receptor; C5AR, C5a receptor; C5L2, C5a-like receptor 2; HMGB1, high-mobility group box 1 protein; IL-17A, interleukin-17A; MAC, membrane-attack complex; MIF, macrophage migration-inhibitory factor; PAR1, protease-activated receptor 1; PRR, pattern-recognition receptor; RAGE, receptor for advanced glycation end-products; TLR4, Toll-like receptor 4.