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 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 neurotransmitter acetylcholine, and the Alpha-7 nicotinic receptor receptor expressed on cytokine-producing cells.[1] The release of acetylcholine in spleen suppresses the production of TNF and other cytokines which cause damaging inflammation.[2] 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 the spleen, where a subset of specialized T cells is activated to secrete acetylcholine.[3] 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, colitis, sepsis, hemorrhagic shock, and congestive heart failure indicate that electrical stimulation of the vagus nerve can prevent or reverse these diseases.[4] 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).

References

  1. ↑ Tracey KJ (June 2009). "Reflex control of immunity". 9 (6): 418–28. doi:10.1038/nri2566. PMID 19461672.
  2. ↑ Rosas-Ballina M, Ochani M, Parrish WR, et al. (August 2008). "Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia". 105 (31): 11008–13. doi:10.1073/pnas.0803237105. PMC 2504833Freely accessible. PMID 18669662.
  3. ↑ Mauricio Rosas-Ballina, Peder S. Olofsson at al. "Acetylcholine-Synthesizing T Cells Relay Neural Signals in a Vagus Nerve Circuit." Science. 2011 Oct 7;334(6052):98-101. PMID 21921156
  4. ↑ Tracey KJ (February 2007). "Physiology and immunology of the cholinergic antiinflammatory pathway". 117 (2): 289–96. doi:10.1172/JCI30555. PMC 1783813Freely accessible. PMID 17273548.
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