TY - JOUR

T1 - Human immune cell mobilization during exercise

T2 - effect of IL-6 receptor blockade

AU - Bay, Marie Lund

AU - Heywood, Sarah

AU - Wedell-Neergaard, Anne Sophie

AU - Schauer, Tim

AU - Lehrskov, Louise Lang

AU - Christensen, Regitse Højgaard

AU - Legård, Grit Elster

AU - Jensen, Peter Østrup

AU - Krogh-Madsen, Rikke

AU - Ellingsgaard, Helga

N1 - Publisher Copyright: © 2020 The Authors. Experimental Physiology © 2020 The Physiological Society

PY - 2020

Y1 - 2020

N2 - New Findings: What is the central question of this study? Does blockade of the IL-6 receptor by tocilizumab inhibit immune cell mobilization to the blood stream in humans during an acute bout of exercise? What is the main finding and its importance? Blockade of IL-6 receptor signalling by tocilizumab attenuates mobilization of NK cells and dendritic cells to the blood stream during exercise. This implies an inhibitory effect of tocilizumab on the innate immune response to physical stress, which could be considered in clinical settings. Abstract: Immune cells are recruited from their storage organs and the endothelial walls to the blood stream in response to physiological stress. This is essential for the recognition and clearing of infected, transformed or damaged cells. One of the most potent stimuli to recruit immune cells to the circulation is exercise. Accordingly, exercise has proven beneficial in disease settings, such as cancer and diabetes. Interleukin-6 (IL-6) is released from contracting skeletal muscle in response to exercise, and rodent studies have established a link between exercise-induced IL-6 and recruitment of natural killer (NK) cells. Whether exercise-induced IL-6 is involved in regulating NK cell mobilization in humans is unclear. This study explored the effect of IL-6 receptor blockade on immune cell mobilization during an acute bout of exercise in humans. In a randomized, placebo-controlled clinical study, abdominally obese humans receiving placebo infusions or tocilizumab infusions performed an acute bout of exercise before and after the intervention. Immune cell recruitment was measured by flow cytometry. IL-6 receptor blockade attenuated the increase of NK cells by 53% (mean difference −0.49 (95% CI: −0.89 to −0.08) × 109 cells L−1, P < 0.001) and dendritic cells by 66% (mean difference −0.14 (95% CI: −0.28 to 0.010) נ109 cells L−1, P < 0.001) induced by an acute bout of exercises. No changes were observed for T cells, monocytes and neutrophils. Treatments which interact with the exercise-mediated immune surveillance provide relevant clinical information in pursuing the ‘exercise as medicine’ concept.

AB - New Findings: What is the central question of this study? Does blockade of the IL-6 receptor by tocilizumab inhibit immune cell mobilization to the blood stream in humans during an acute bout of exercise? What is the main finding and its importance? Blockade of IL-6 receptor signalling by tocilizumab attenuates mobilization of NK cells and dendritic cells to the blood stream during exercise. This implies an inhibitory effect of tocilizumab on the innate immune response to physical stress, which could be considered in clinical settings. Abstract: Immune cells are recruited from their storage organs and the endothelial walls to the blood stream in response to physiological stress. This is essential for the recognition and clearing of infected, transformed or damaged cells. One of the most potent stimuli to recruit immune cells to the circulation is exercise. Accordingly, exercise has proven beneficial in disease settings, such as cancer and diabetes. Interleukin-6 (IL-6) is released from contracting skeletal muscle in response to exercise, and rodent studies have established a link between exercise-induced IL-6 and recruitment of natural killer (NK) cells. Whether exercise-induced IL-6 is involved in regulating NK cell mobilization in humans is unclear. This study explored the effect of IL-6 receptor blockade on immune cell mobilization during an acute bout of exercise in humans. In a randomized, placebo-controlled clinical study, abdominally obese humans receiving placebo infusions or tocilizumab infusions performed an acute bout of exercise before and after the intervention. Immune cell recruitment was measured by flow cytometry. IL-6 receptor blockade attenuated the increase of NK cells by 53% (mean difference −0.49 (95% CI: −0.89 to −0.08) × 109 cells L−1, P < 0.001) and dendritic cells by 66% (mean difference −0.14 (95% CI: −0.28 to 0.010) נ109 cells L−1, P < 0.001) induced by an acute bout of exercises. No changes were observed for T cells, monocytes and neutrophils. Treatments which interact with the exercise-mediated immune surveillance provide relevant clinical information in pursuing the ‘exercise as medicine’ concept.

KW - dendritic cells

KW - exercise

KW - interleukin-6

KW - NK cells

KW - tocilizumab

U2 - 10.1113/EP088864

DO - 10.1113/EP088864

M3 - Journal article

C2 - 33006190

AN - SCOPUS:85092596129

VL - 105

SP - 2086

EP - 2098

JO - Experimental Physiology

JF - Experimental Physiology

SN - 0958-0670

IS - 12

ER -