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 Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in autocrin ...

, and a motor or efferent arc, which transmits action potentials in the

vagus nerve The vagus nerve, also known as the tenth cranial nerve, cranial nerve X, or simply CN X, is a cranial nerve that interfaces with the parasympathetic control of the heart, lungs, and digestive tract. It comprises two nerves—the left and right ...

to suppress cytokine production. Increased signaling in the efferent arc inhibits inflammation and prevents organ damage. It has also been shown that the brain can use this circuit not only to regulate the

immune response An immune response is a reaction which occurs within an organism for the purpose of defending against foreign invaders. These invaders include a wide variety of different microorganisms including viruses, bacteria, parasites, and fungi which could ...

but also to extend the

immunological memory Immunological memory is the ability of the immune system to quickly and specifically recognize an antigen that the body has previously encountered and initiate a corresponding immune response. Generally, these are secondary, tertiary and other subs ...

Molecular mechanism

The molecular basis of cytokine-inhibiting signals requires the

neurotransmitter A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a synapse. The cell receiving the signal, any main body part or target cell, may be another neuron, but could also be a gland or muscle cell. Neuro ...

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

, and the

Alpha-7 nicotinic receptor The alpha-7 nicotinic receptor, also known as the α7 receptor, is a type of nicotinic acetylcholine receptor implicated in long-term memory, consisting entirely of α7 subunits.Pharmacology, (Rang, Dale, Ritter & Moore, , 5th ed., Churchill Liv ...

receptor expressed on cytokine-producing cells. The release of

in spleen suppresses the production of TNF and other cytokines which causes 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 The innate, or nonspecific, immune system is one of the two main immunity strategies (the other being the adaptive immune system) in vertebrates. The innate immune system is an older evolutionary defense strategy, relatively speaking, and is the ...

response to invasion and injury. The action potentials that arise in the vagus nerve are transmitted to the

spleen The spleen is an organ found in almost all vertebrates. Similar in structure to a large lymph node, it acts primarily as a blood filter. The word spleen comes .

, where a subset of specialized T cells are activated to secrete acetylcholine. The net effect of the reflex is to prevent the damage caused by excessive cytokine production.

Therapeutic potential

Evidence from experimental disease models of

arthritis Arthritis is a term often used to mean any disorder that affects joints. Symptoms generally include joint pain and stiffness. Other symptoms may include redness, warmth, swelling, and decreased range of motion of the affected joints. In som ...

colitis Colitis is swelling or inflammation of the large intestine ( colon). Colitis may be acute and self-limited or long-term. It broadly fits into the category of digestive diseases. In a medical context, the label ''colitis'' (without qualification) ...

sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is follo ...

hemorrhagic shock Hypovolemic shock is a form of shock caused by severe hypovolemia (insufficient blood volume or extracellular fluid in the body). It could be the result of severe dehydration through a variety of mechanisms or blood loss. Hypovolemic shock is a ...

, and

congestive heart failure Heart failure (HF), also known as congestive heart failure (CHF), is a syndrome, a group of signs and symptoms caused by an impairment of the heart's blood pumping function. Symptoms typically include shortness of breath, excessive fatigue, a ...

indicate that electrical stimulation of the vagus nerve can prevent or reverse these diseases. Some research suggests that it is possible to implant nerve stimulants to replace

anti-inflammatory drugs Non-steroidal anti-inflammatory drugs (NSAID) are members of a Indication (medicine), therapeutic drug class which Analgesic, reduces pain, Anti-inflammatory, decreases inflammation, Antipyretic, decreases fever, and Antithrombotic, prevents blo ...

that target cytokine activity (e.g. anti-TNF and anti-IL-1 antibodies).

References

{{reflist Immunology Neurophysiology

Molecular mechanism

Therapeutic potential

See also

References