Cholinergic anti-inflammatory pathway
Encyclopedia
The Cholinergic Anti-inflammatory Pathway regulates the innate immune response (Innate immunity) to injury, pathogens, and tissue ischemia. It is the efferent, or motor arm of the Inflammatory Reflex
, the neural circuit that responds to and regulates the inflammatory response.
Tumor Necrosis Factor (TNF) (and other cytokines) are produced by cells of the innate immune system during local injury and infection. These contribute to initiating a cascade of mediator release, and recruiting inflammatory cells to the site of infection to contain infection, referred to as "innate immunity.". TNF amplifies and prolongs the inflammatory response by activating other cells to release interleukin-1 (IL-1), high mobility group
B1 (HMGB1
) and other cytokines. These inflammatory cytokine responses confer protective advantages to the host at the site of bacterial infection
. A “beneficial” inflammatory response is limited, resolves in 48-72 hours, and does not spread systemically. The cholinergic anti-inflammatory pathway provides a braking effect on the innate immune response which protects the body against the damage that can occur if a localized inflammatory response spreads beyond the local tissues, which results in toxicity or damage to the kidney
, liver
, lungs, and other organs.
is the tenth cranial nerve. It regulates heart rate
, bronchoconstriction, digestion, and the innate immune response. The vagus nerve innervates the celiac ganglion, the site of origin of the splenic nerve. Stimulation of the efferent vagus nerve slows heart rate, induces gastric motility, and inhibits TNF production in spleen. Stimulation of the efferent pathway of the vagus nerve releases acetylcholine, the neurotransmitter which interacts with the α7 subunit of the nicotinic AChR
(α7 nAChR). nAChR is expressed on the cell membrane
of macrophages and other cytokine secreting cells. Binding of acetylcholine to nAChR activates intracellular signal transduction which inhibits release of pro-inflammatory cytokines. Ligand receptor signaling does suppress production of anti-inflammatory cytokines (IL-10).
Inflammatory reflex
The inflammatory reflex is a neural circuit that regulates the immune response to injury and invasion. All reflexes have an afferent and efferent arc. The Inflammatory reflex has a sensory, afferent arc, which is activated by cytokines, and a motor, or efferent arc, which transmits action...
, the neural circuit that responds to and regulates the inflammatory response.
Regulating the Immune Response
For the first time (in 1987) in experiment it has been shown that armin (nonreversible inhibitor of acetylcholinesterase) at their injection 24 h prior to sepsis modelling invoke essential depression of a lethality of mice from experimental infectious process. Later (in 1995) this data has been confirmed at cholinergic stimulation by other cholinomimetics.Tumor Necrosis Factor (TNF) (and other cytokines) are produced by cells of the innate immune system during local injury and infection. These contribute to initiating a cascade of mediator release, and recruiting inflammatory cells to the site of infection to contain infection, referred to as "innate immunity.". TNF amplifies and prolongs the inflammatory response by activating other cells to release interleukin-1 (IL-1), high mobility group
High mobility group
High-Mobility Group or HMG is a group of chromosomal proteins that help withtranscription, replication, recombination, and DNA repair.-Families:The HMG proteins are subdivided into 3 superfamilies each containing a characteristic functional domain:...
B1 (HMGB1
HMGB1
High-mobility group protein B1, also known as high-mobility group protein 1 and amphoterin, is a protein that in humans is encoded by the HMGB1 gene.HMG-1 belongs to high mobility group.-Role in Inflammation:...
) and other cytokines. These inflammatory cytokine responses confer protective advantages to the host at the site of bacterial infection
Infection
An infection is the colonization of a host organism by parasite species. Infecting parasites seek to use the host's resources to reproduce, often resulting in disease...
. A “beneficial” inflammatory response is limited, resolves in 48-72 hours, and does not spread systemically. The cholinergic anti-inflammatory pathway provides a braking effect on the innate immune response which protects the body against the damage that can occur if a localized inflammatory response spreads beyond the local tissues, which results in toxicity or damage to the kidney
Kidney
The kidneys, organs with several functions, serve essential regulatory roles in most animals, including vertebrates and some invertebrates. They are essential in the urinary system and also serve homeostatic functions such as the regulation of electrolytes, maintenance of acid–base balance, and...
, liver
Liver
The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...
, lungs, and other organs.
Neurophysiological and Immunological Mechanism
The Vagus NerveVagus nerve
The vagus nerve , also called pneumogastric nerve or cranial nerve X, is the tenth of twelve paired cranial nerves...
is the tenth cranial nerve. It regulates heart rate
Heart rate
Heart rate is the number of heartbeats per unit of time, typically expressed as beats per minute . Heart rate can vary as the body's need to absorb oxygen and excrete carbon dioxide changes, such as during exercise or sleep....
, bronchoconstriction, digestion, and the innate immune response. The vagus nerve innervates the celiac ganglion, the site of origin of the splenic nerve. Stimulation of the efferent vagus nerve slows heart rate, induces gastric motility, and inhibits TNF production in spleen. Stimulation of the efferent pathway of the vagus nerve releases acetylcholine, the neurotransmitter which interacts with the α7 subunit of the nicotinic AChR
Nicotinic acetylcholine receptor
Nicotinic acetylcholine receptors, or nAChRs, are cholinergic receptors that form ligand-gated ion channels in the plasma membranes of certain neurons and on the postsynaptic side of the neuromuscular junction...
(α7 nAChR). nAChR is expressed on the cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
of macrophages and other cytokine secreting cells. Binding of acetylcholine to nAChR activates intracellular signal transduction which inhibits release of pro-inflammatory cytokines. Ligand receptor signaling does suppress production of anti-inflammatory cytokines (IL-10).