Internal medicine

Neuroscience

Receptor

Cholinergic

Afferent

Vagus nerve stimulation

Vagus nerve

Biology

Nicotinic agonist

Choline acetyltransferase

Efferent

Stimulation

Acetylcholine

Medicine

Reflex

Pharmacology

Cell Reports Medicine

The cholinergic anti-inflammatory pathway is the efferent arm of the inflammatory reflex, a neural circuit through which the CNS can modulate peripheral immune responses. Signals communicated via the vagus and splenic nerves use acetylcholine, produced by Choline acetyltransferase (ChAT)+ T cells, to downregulate the inflammatory actions of macrophages expressing α7 nicotinic receptors. Pre-clinical studies using transgenic animals, cholinergic agonists, vagotomy, and vagus nerve stimulation have demonstrated this pathway's role and therapeutic potential in numerous inflammatory diseases. In this review, we summarize what is understood about the inflammatory reflex. We also demonstrate how pre-clinical findings are being translated into promising clinical trials, and we draw particular attention to innovative bioelectronic methods of harnessing the cholinergic anti-inflammatory pathway for clinical use.

Manipulation of the inflammatory reflex as a therapeutic strategy