title: Acute stress elicited by bungee jumping suppresses human innate immunity.
abstract: Although a relation between diminished human immunity and stress is well recognized both within the general public and the scientific literature, the molecular mechanisms by which stress alters immunity remain poorly understood. We explored a novel model for acute human stress involving volunteers performing a first-time bungee jump from an altitude of 60 m and exploited this model to characterize the effects of acute stress in the peripheral blood compartment. Twenty volunteers were included in the study; half of this group was pretreated for 3 d with the β-receptor blocking agent propranolol. Blood was drawn 2 h before, right before, immediately after and 2 h after the jump. Plasma catecholamine and cortisol levels increased significantly during jumping, which was accompanied by significantly reduced ex vivo inducibility of proinflammatory cytokines as well as activation of coagulation and vascular endothelium. Kinome profiles obtained from the peripheral blood leukocyte fraction contained a strong noncanonical glucocorticoid receptor signal transduction signature after jumping. In apparent agreement, jumping down-regulated Lck/Fyn and cellular innate immune effector function (phagocytosis). Pretreatment of volunteers with propranolol abolished the effects of jumping on coagulation and endothelial activation but left the inhibitory effects on innate immune function intact. Taken together, these results indicate that bungee jumping leads to a catecholamine-independent immune suppressive phenotype and implicate noncanonical glucocorticoid receptor signal transduction as a major pathway linking human stress to impaired functioning of the human innate immune system.
authors.affiliation: Department of Intensive Care Medicine, University of Amsterdam, Amsterdam, the Netherlands. d.j.vanwesterloo@amc.uva.nl
authors.forename: David J
authors.initials: DJ
authors.lastname: van Westerloo
authors.forename: Goda
authors.initials: G
authors.lastname: Choi
authors.forename: Ester C
authors.initials: EC
authors.lastname: Löwenberg
authors.forename: Jasper
authors.initials: J
authors.lastname: Truijen
authors.forename: Alex F
authors.initials: AF
authors.lastname: de Vos
authors.forename: Erik
authors.initials: E
authors.lastname: Endert
authors.forename: Joost C M
authors.initials: JC
authors.lastname: Meijers
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Manuel P F L
authors.initials: MP
authors.lastname: Pereira
authors.forename: Karla C S
authors.initials: KC
authors.lastname: Queiroz
authors.forename: Sander H
authors.initials: SH
authors.lastname: Diks
authors.forename: Marcel
authors.initials: M
authors.lastname: Levi
authors.forename: Maikel P
authors.initials: MP
authors.lastname: Peppelenbosch
authors.forename: Tom
authors.initials: T
authors.lastname: van der Poll
mesh_terms: D000293:Adolescent; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000328:Adult; D000531:Altitude; D001777:Blood Coagulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002395:Catecholamines / Q000097:blood; D016207:Cytokines / Q000378:metabolism; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D006854:Hydrocortisone / Q000097:blood; D007113:Immunity, Innate / Q000187:drug effects / Q000502:physiology*; D007958:Leukocyte Count; D007962:Leukocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D010770:Phosphotransferases / Q000378:metabolism; D011433:Propranolol / Q000494:pharmacology; D011446:Prospective Studies; D015398:Signal Transduction / Q000187:drug effects; D013177:Sports; D013312:Stress, Physiological / Q000502:physiology*; D055815:Young Adult
chemical_list: D000319:Adrenergic beta-Antagonists; D002395:Catecholamines; D016207:Cytokines; D008070:Lipopolysaccharides; D011433:Propranolol; D010770:Phosphotransferases; D006854:Hydrocortisone