title: Voluntary activation of the sympathetic nervous system and attenuation of the innate immune response in humans.
abstract: Excessive or persistent proinflammatory cytokine production plays a central role in autoimmune diseases. Acute activation of the sympathetic nervous system attenuates the innate immune response. However, both the autonomic nervous system and innate immune system are regarded as systems that cannot be voluntarily influenced. Herein, we evaluated the effects of a training program on the autonomic nervous system and innate immune response. Healthy volunteers were randomized to either the intervention (n = 12) or control group (n = 12). Subjects in the intervention group were trained for 10 d in meditation (third eye meditation), breathing techniques (i.a., cyclic hyperventilation followed by breath retention), and exposure to cold (i.a., immersions in ice cold water). The control group was not trained. Subsequently, all subjects underwent experimental endotoxemia (i.v. administration of 2 ng/kg Escherichia coli endotoxin). In the intervention group, practicing the learned techniques resulted in intermittent respiratory alkalosis and hypoxia resulting in profoundly increased plasma epinephrine levels. In the intervention group, plasma levels of the anti-inflammatory cytokine IL-10 increased more rapidly after endotoxin administration, correlated strongly with preceding epinephrine levels, and were higher. Levels of proinflammatory mediators TNF-α, IL-6, and IL-8 were lower in the intervention group and correlated negatively with IL-10 levels. Finally, flu-like symptoms were lower in the intervention group. In conclusion, we demonstrate that voluntary activation of the sympathetic nervous system results in epinephrine release and subsequent suppression of the innate immune response in humans in vivo. These results could have important implications for the treatment of conditions associated with excessive or persistent inflammation, such as autoimmune diseases.
authors.affiliation: Intensive Care Medicine,Anesthesiology,Nijmegen Institute for Infection, Inflammation and Immunity, and matthijs.kox@radboudumc.nl.
authors.forename: Matthijs
authors.initials: M
authors.lastname: Kox
authors.affiliation: Intensive Care Medicine,Nijmegen Institute for Infection, Inflammation and Immunity, and.
authors.forename: Lucas T
authors.initials: LT
authors.lastname: van Eijk
authors.affiliation: Intensive Care Medicine,Nijmegen Institute for Infection, Inflammation and Immunity, and.
authors.forename: Jelle
authors.initials: J
authors.lastname: Zwaag
authors.affiliation: Intensive Care Medicine,Nijmegen Institute for Infection, Inflammation and Immunity, and.
authors.forename: Joanne
authors.initials: J
authors.lastname: van den Wildenberg
authors.affiliation: Laboratory Medicine, Radboud University Medical Centre, Geert Grooteplein 10, 6500 HB, Nijmegen, The Netherlands.
authors.forename: Fred C G J
authors.initials: FC
authors.lastname: Sweep
authors.affiliation: Intensive Care Medicine,Nijmegen Institute for Infection, Inflammation and Immunity, and.
authors.forename: Johannes G
authors.initials: JG
authors.lastname: van der Hoeven
authors.affiliation: Intensive Care Medicine,Nijmegen Institute for Infection, Inflammation and Immunity, and.
authors.forename: Peter
authors.initials: P
authors.lastname: Pickkers
mesh_terms: D000328:Adult; D002395:Catecholamines / Q000097:blood; D003080:Cold Temperature; D004731:Endotoxins / Q000737:chemistry; D004837:Epinephrine / Q000097:blood; D064368:Healthy Volunteers; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D000860:Hypoxia; D007113:Immunity, Innate / Q000502:physiology*; D007249:Inflammation; D016753:Interleukin-10 / Q000097:blood; D015850:Interleukin-6 / Q000097:blood; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D019122:Meditation; D012119:Respiration; D013564:Sympathetic Nervous System / Q000502:physiology*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D055815:Young Adult
chemical_list: D002395:Catecholamines; D004731:Endotoxins; D015850:Interleukin-6; D016209:Interleukin-8; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; C044101:endotoxin, Escherichia coli; D006854:Hydrocortisone; D004837:Epinephrine
keywords: LPS; cathecholamines; cortisol