Inflammatory reflex
Encyclopedia
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 potentials in the vagus nerve to suppress cytokine production. Increased signaling in the efferent arc inhibits inflammation and prevents organ damage.
acetylcholine
, and the Alpha-7 nicotinic receptor
receptor expressed on cytokine-producing cells. The release of acetylcholine
in spleen suppresses the production of TNF and other cytokines which cause damaging inflammation. Signaling in the efferent arc of the inflammatory reflex, termed the "Cholinergic anti-inflammatory pathway
," provides a regulatory check on the innate immune system
response to invasion and injury. The action potentials arising in the vagus nerve are transmitted to spleen, where a subset of specialized T cells is activated to secrete acetylcholine. The net effect if the the reflex is to prevent the damage caused by excessive cytokine production.
, colitis
, sepsis, hemorrhagic shock, and congestive heart failure
indicate that electrical stimulation of the vagus nerve can prevent or reverse these diseases. It may be possible to implant nerve stimulators to replace anti-inflammatory drugs that target cytokine activity (e.g. anti-TNF and anti-IL-1 antibodies).
Afferent
Afferent is an anatomical term with the following meanings:*Conveying towards a center, for example the afferent arterioles conveying blood towards the Bowman's capsule in the Kidney. Opposite to Efferent.*Something that so conducts, see Afferent nerve fiber...
arc, which is activated by cytokines, and a motor, or efferent
Efferent
Efferent is an anatomical term with the following meanings:*Conveying away from a center, for example the efferent arterioles conveying blood away from the Bowman's capsule in the kidney. Opposite to afferent....
arc, which transmits action potentials in the vagus nerve to suppress cytokine production. Increased signaling in the efferent arc inhibits inflammation and prevents organ damage.
Molecular mechanism
The molecular basis of cytokine-inhibiting signals requires the neurotransmitterNeurotransmitter
Neurotransmitters are endogenous chemicals that transmit signals from a neuron to a target cell across a synapse. Neurotransmitters are packaged into synaptic vesicles clustered beneath the membrane on the presynaptic side of a synapse, and are released into the synaptic cleft, where they bind to...
acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
, and the Alpha-7 nicotinic receptor
Alpha-7 nicotinic receptor
The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor, consisting entirely of α7 subunits....
receptor expressed on cytokine-producing cells. The release of acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
in spleen suppresses the production of TNF and other cytokines which cause damaging inflammation. Signaling in the efferent arc of the inflammatory reflex, termed the "Cholinergic anti-inflammatory pathway
Cholinergic anti-inflammatory pathway
The Cholinergic Anti-inflammatory Pathway regulates the innate immune response 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.- Regulating the Immune Response :For...
," provides a regulatory check on the innate immune system
Innate immune system
The innate immune system, also known as non-specific immune system and secondary line of defence, comprises the cells and mechanisms that defend the host from infection by other organisms in a non-specific manner...
response to invasion and injury. The action potentials arising in the vagus nerve are transmitted to spleen, where a subset of specialized T cells is activated to secrete acetylcholine. The net effect if the the reflex is to prevent the damage caused by excessive cytokine production.
Therapeutic potential
Evidence from experimental disease models of arthritisArthritis
Arthritis is a form of joint disorder that involves inflammation of one or more joints....
, colitis
Colitis
In medicine, colitis refers to an inflammation of the colon and is often used to describe an inflammation of the large intestine .Colitides may be acute and self-limited or chronic, i.e...
, sepsis, hemorrhagic shock, and congestive heart failure
Congestive heart failure
Heart failure often called congestive heart failure is generally defined as the inability of the heart to supply sufficient blood flow to meet the needs of the body. Heart failure can cause a number of symptoms including shortness of breath, leg swelling, and exercise intolerance. The condition...
indicate that electrical stimulation of the vagus nerve can prevent or reverse these diseases. It may be possible to implant nerve stimulators to replace anti-inflammatory drugs that target cytokine activity (e.g. anti-TNF and anti-IL-1 antibodies).