Kevin J. Tracey
Laboratory of Biomedical Science, North Shore-LIJ Research Institute, 350 Community Drive, Manhasset, New York 11030, USA (e-mail: firstname.lastname@example.org)
Inflammation is a local, protective response to microbial invasion or injury. It must be fine-tuned and
regulated precisely, because deficiencies or excesses of the inflammatory response cause morbidity and shorten lifespan. The discovery that cholinergic neurons inhibit acute inflammation has qualitatively expanded our understanding of how the nervous system modulates immune responses. The nervous system reflexively regulates the inflammatory response in real time, just as it controls heart rate and other vital functions. The opportunity now exists to apply this insight to the treatment of inflammation through selective and reversible ‘hard-wired’ neural systems.
“The mind has great influence over the body, and maladies often have their origin there.” Molière (1622–1673).
survival is impossible without vigilant defence against attack and injury. The innate immune
system continuously surveys the body for the presence of invaders. When it encounters an
attack, it involuntarily sets in motion a discrete, localized inflammatory response to thwart most
pathogenic threats. The magnitude of the inflammatory response is crucial: insufficient responses result in immunodeficiency, which can lead to infection and cancer; excessive responses cause morbidity and mortality in diseases such as rheumatoid arthritis, Crohn’s disease, atherosclerosis, diabetes, Alzheimer’s disease, multiple sclerosis, and cerebral and myocardial ischaemia. If inflammation spreads into the bloodstream, as occurs in septic shock syndrome, sepsis, meningitis and severe trauma, the inflammatory responses can be more
dangerous than the original inciting stimulus. Homeostasis and health are restored when inflammation is limited by anti-inflammatory responses that are redundant, rapid, reversible, localized, adaptive to changes in input and integrated by the nervous system.