Inflammatory reflex

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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[edit]

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. The net effect of the reflex is to prevent the damage caused by excessive cytokine production.[3]

Therapeutic potential[edit]

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).[5]

References[edit]

  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. 
  5. ^ "The shock tactics set to shake up immunology".