Table 1: Summary of immunomodulatory effects of neurotransmitters.

Neurotransmitter ReceptorCell source of neurotransmitterEffects of receptor activation in intestinal disease

AcetylcholineNicotinic acetylcholine receptors
Muscarinic acetylcholine receptors
MultipleVagotomy ameliorates colitis [68]
Variable outcomes of nicotinic agonists on the course of colitis [51]
Vagal nerve stimulation ameliorates intestinal inflammation:
Postoperative ileus, [69] septic ileus
Intestinal barrier breakdown [70]
Mast cell activation [28]
Ischemia reperfusion injury

Dopamine, adrenaline, and noradrenalineDopamine receptors,
adrenergic receptors a and b
CNS neurons
Recruited
immune cells
Postganglionic Nerves throughout the GI tract
Potent inhibitor of Th1 and macrophage functions
Multiple effects on cytokine and chemokine secretion
(reviewed a.o. in [30, 32, 71])
In APCs an decrease of
IL-12 Type 1, proinflammatory
TNF-a Type 1, proinflammatory
IFN-g Type 1, proinflammatory
IL-2 Type 1
IL-1 Proinflammatory
IL-4 Type 2, anti-inflammatory
IL-3 Hemopoietic factor
GM-Hemopoietic factor CSF
MIP-1 -Proinflammatory chemokine
In APCs an increase of
IL-10 Type 2, anti-inflammatory
TGF-a Type 2, anti-inflammatory
IL-8 Proinflammatory
Chemotactic for neutrophils, macrophages, and T lymphocytes [72]
Promotes the development of the precursors of granulocytes and macrophages [73]

Vasoactive intestinal peptide VPAC1
VPAC2
Recruited immune cells
Enteric nerve plexus
Lamina propria nerves
CNS
Amelioration of TNBS-induced colitis by shifting T-cell responses from Th1 to Th2 [74].
Generation of tolerogenic dendritic cells [75]

Substance PNK-1R
NK-2R
NK-3R
Recruited immune cells, lamina propria macrophages, colonic glia
Motor neurons of
intestinal muscularis
Lamina propria nerves
CNS
Antagonists ameliorate disease in a rat model
of TNBS-induced colitis [76]
NK-1R−/− mice protected from inflammatory diarrhoea in C. difficile toxin A [77]
Proinflammatory activation of myeloid cells

Neuropeptide Y
Peptide YY
Pancreatic polypeptide
6 Y receptors (Y1-6R)CNS
Mononuclear blood leukocytes
T cells, APCs
Enhanced T-cell cytokine release
Reduced APC cytokine release and function [78, 79]