Abstract

BackgroundHelium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific “conditioning” protocols. Before widespread use of this “conditioning” agent in clinical practice, negative side effects have to be ruled out. We investigated the effect of prolonged helium inhalation on the responsiveness of the human immune response in whole blood ex vivo.MethodsMale healthy volunteers inhaled 30 minutes heliox (79%He/21%O2) or air in a cross over design, with two weeks between measurements. Blood was withdrawn at T0 (baseline), T1 (25 min inhalation) and T2-T5 (1, 2, 6, 24 h after inhalation) and incubated with lipopolysaccharide (LPS), lipoteichoic acid (LTA), T-cell stimuli anti-CD3/ anti-CD28 (TCS) or RPMI (as control) for 2, 4 and 24 hours or not incubated (0 h). An additional group of six volunteers inhaled 60 minutes of heliox or air, followed by blood incubation with LPS and RPMI. Tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), interleukin-6 (IL-6), interleukin-8 (IL-8), interferon-γ (IFN-γ) and interleukin-2 (IL-2) was analyzed by cytometric bead array. Statistical analysis was performed by the Wilcoxon test for matched samples.ResultsIncubation with LPS, LTA or TCS significantly increased TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone. Thirty min of helium inhalation did not influence the amounts of TNF-α, IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to air. Sixty min of helium inhalation did not affect cytokine production after LPS stimulation.ConclusionsWe conclude that 79% helium inhalation does not affect the responsiveness of the human immune system in healthy volunteers.Trial registrationDutch Trial Register: http://www.trialregister.nl/ NTR2152

Highlights

  • Helium inhalation protects myocardium, brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific “conditioning” protocols

  • Helium inhalation does not influence leukocyte and lymphocyte counts At baseline, there was no difference in C-reactive protein between the 30 min inhalation groups; 1.6 ± 0.4 and 2.3 ± 0.6 in the helium and air group

  • Ex vivo stimulation of whole blood with LPS, lipoteichoic acid (LTA) or T-cell stimuli anti-CD3/ anti-CD28 (TCS) significantly increased Tumor necrosis factor-α (TNF-α), IL-1β, IL-6, IL-8, IFN-γ and IL-2 in comparison to incubation with RPMI alone After 2, 4 and 24 hours of incubation with LPS, the amount of TNF-α was significantly higher in comparison to incubation with RPMI alone, see Figure 1

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Summary

Introduction

Brain and endothelium against ischemia/reperfusion injury in animals and humans, when applied according to specific “conditioning” protocols. The innate immune response involves monocytes, neutrophils, dendritic cells and macrophages and parenchymal cells such as epithelial and endothelial cells. Secretion of cytokines and chemokines results in monocyte and neutrophil migration to inflamed tissues and antigen presentation. This initial and aspecific cascade induces secondary antigen specific events known as the adaptive immune system involving T- and B-lymphocytes. Volatile anesthetics and xenon exert immunomodulatory effects by affecting endothelial expression of adhesion molecules and the secretion of cytokines and chemokines [10] as well as lymphocytes [11,12,13]

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