The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway and implications for therapy


Jared M. Huston, MD, Department of Surgery, Stony Brook University Medical Center, T18-040, Health Sciences Center, Stony Brook, NY 11794, USA.
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Huston JM, Tracey KJ (Department of Surgery, Division of General Surgery, Trauma, Surgical Critical Care, and Burns, Stony Brook University Medical Center, Health Sciences Center, Stony Brook; and Laboratory of Biomedical Science, The Feinstein Institute for Medical Research, Manhasset; NY, USA). The pulse of inflammation: heart rate variability, the cholinergic anti-inflammatory pathway, and implications for therapy (Key Symposium). J Intern Med 2011; 269: 45–53.

Abstract.  Biological therapeutics targeting TNF, IL-1 and IL-6 are widely used for treatment of rheumatoid arthritis, inflammatory bowel disease and a growing list of other syndromes, often with remarkable success. Now advances in neuroscience have collided with this therapeutic approach, perhaps rendering possible the development of nerve stimulators to inhibit cytokines. Action potentials transmitted in the vagus nerve culminate in the release of acetylcholine that blocks cytokine production by cells expressing acetylcholine receptors. The molecular mechanism of this cholinergic anti-inflammatory pathway is attributable to signal transduction by the nicotinic alpha 7 acetylcholine receptor subunit, a regulator of the intracellular signals that control cytokine transcription and translation. Favourable preclinical data support the possibility that nerve stimulators may be added to the future therapeutic armamentarium, possibly replacing some drugs to inhibit cytokines.