Bungee jumping-related stress and innate immunity
In this study, David van Westerloo and colleagues from the University of Amsterdam report that bungee jumping resulted in a time-dependent increase in the plasma concentrations of epinephrine, norepinephrine and cortisol; decreased whole blood production of TNF-alpha and IL-8, and a substantial reduction of bacterial phagocytosis by granulocytes and monocytes.
The authors of this study hypothesised 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.
Bungee jumping may represent an interesting and natural model for stress research in humans. High-altitude jumping seems to be associated with a substantial stimulation of the stress or fight-or-flight response.
Twenty healthy male volunteers, naive to bungee jumping or skydiving and aged between 18 and 35 years, were included in the study. The authors performed ex vivo stimulation of whole blood with LPS (from Escherichia coli 0111:B4) and measured the levels of tumor necrosis factor (TNF)-α (a proinflammatory cytokine), interleukin (IL)-8 (a chemokine) and IL-10 (an anti-inflammatory cytokine) in stimulated blood samples.
The results indicated that bungee jumping resulted in a time-dependent increase in the plasma concentrations of both epinephrine (adrenaline) and norepinephrine (noradrenaline) directly before the jump in both groups. A sharp decrease in epinephrine levels was observed directly after the bungee jump, whereas norepinephrine concentrations remained elevated longer. Cortisol levels remained unaltered before the jump but increased significantly during the jump. Propranolol did not influence the release of catecholamines or cortisol.
Of note, bungee jumping was associated with a decreased capacity of whole blood leukocytes to release TNF-α and IL-8, which was already apparent directly before the jump. However, levels of IL-10 induction remained unaltered during the study. The reduced capacity to release TNF-α and IL-8 was not inhibited by pretreatment with propranolol. Thus, in this study pretreatment of volunteers with the beta-adrenoreceptor antagonist propranolol left the inhibitory effects on innate immune function intact.
Thus, since the authors found that inhibition of ex vivo release of cytokines after bungee jumping was not related to the release of catecholamines, they further investigated the molecular basis of suppressed immunity after bungee jumping. For this, a kinome profile was constructed before and after bungee jumping in untreated volunteers (control group). Kinome profiles were generated by incubating lysates of samples obtained from volunteer peripheral blood 2 h before jumping with those obtained directly after the jump, using arrays exhibiting 976 different kinase substrates and 33P-γ-ATP.
Comprehensive descriptions of mammalian kinomes have become possible through the sequential spotting of kinase substrates, encompassing the entire human kinome, on a carrier. When such peptide arrays are incubated with cellular lysates and radioactive ATP, kinases active in the lysate will phosphorylate their respective substrates, and upon determining substrate phosphorylation using a phosphoimager, comprehensive descriptions of cellular signaling may be generated.
Kinome profile analysis revealed that Fyn inhibition by noncanonical (also termed nongenomic) glucocorticoid signaling most likely mediates the inhibition of innate immunity observed after the jump.
Classically, glucocorticoid effects are explained from their effects on gene transcription via receptor translocation to the nucleus and altered transactivation of glucocorticoid response elements containing promoters.
Interestingly, a study from 1994 reported an increase of more than 200% in beta-endorphin immunoreactivity after bungee jumping. In contrast to levels of cortisol, the concentration of beta-endorphin recorded immediately after the jump was significantly correlated with ratings on euphoria obtained at subsequent measurements indicating a relationship between beta-endorphins and euphoria. Thus, it is not known whether the increase in the beta-endorphin release may also affect some aspects of innate immunity, as discussed in the Molecular Medicine report.
The authors of this study suggest that the stress response associated with bungee jumping leads to a catecholamine-independent immune suppressive phenotype, and that the activation of noncanonical glucocorticoid signaling in the leukocyte compartment may represent a hallmark of the response to acute stress in humans.
SOURCE: Mol Med 2011, 17:180. doi: 10.2119/molmed.2010.00204. Epub 2010 Dec 10
