Acute Stress Elicited by Bungee Jumping Suppresses Human Innate Immunity

David J Van Westerloo,Lu Zhou,Alex F De Vos,Ester C Löwenberg,Joost C M Meijers,Marcel Levi,Goda Choi,Karla C S Queiroz,Sander H Diks,Tom Van Der Poll,Jasper Truijen,Maikel P Peppelenbosch,Erik Endert,Manuel P F L Pereira

doi:10.2119/molmed.2010.00204

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.

Highlights

It is well recognized that cognitive perception of the environment is a major determinant of immune function, and conditions loosely grouped under the common denominator of stress are perceived as a significant risk factor for infection and autoimmunity [1,2,3]
In this study, we evaluated whether an acute severe stress response induced by bungee jumping suppresses key inflammatory responses involved in the innate immune response to infection
We evaluated the potential role of catecholamines by pretreating half of our study population with the β-receptor antagonist propranolol

Summary

Introduction

It is well recognized that cognitive perception of the environment is a major determinant of immune function, and conditions loosely grouped under the common denominator of stress are perceived as a significant risk factor for infection and autoimmunity [1,2,3]. Stress presumably interacts with immunity owing to the release of stress hormones such as catecholamines and cortisol. Epinephrine, norepinephrine and cortisol in general may result in antiinflammatory effects. These antiinflammatory properties have been reproduced experimentally in humans using the model of intravenous injection of lipopolysaccharide (LPS) [5,6,7,8]. We postulated that acute stress-induced release of stress hormones causes an immune suppressive phenotype and aimed to investigate this by using a novel human model of acute stress. Practical and ethical considerations hamper investigations on the effects of severe stress on human immunity, and there is a need for an ethically acceptable human model that produces severe stress with moderate intraindividual variation. A recent study showed that during height exposure in all participants, fear, dizziness and body

Methods

Results

Conclusion