IL-6 Activity is Required for Maximal Catecholamine Release During High-Intensity Exercise in Men
Andreas K Ziegler1, Tim Schauer2, Sara F Myrup2
1The Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; Department of Clinical Biochemistry, Copenhagen University Hospital Hvidovre, Hvidovre, Copenhagen, Denmark.
Molecular Metabolism
|June 10, 2026
Summary
Interleukin-6 (IL-6) acts as a key signal during intense exercise, linking muscle activity to the body's stress response. Blocking the IL-6 receptor impairs metabolic and immune reactions, highlighting IL-6's role in coordinating fight-or-flight responses.
Area of Science:
- Exercise Physiology
- Endocrinology
- Immunology
Background:
- High-intensity exercise activates complex metabolic, endocrine, and immune systems.
- Interleukin-6 (IL-6) is a proposed mediator linking skeletal muscle activity to systemic stress responses during exercise.
- The precise role of IL-6 in integrating these responses remains unclear.
Purpose of the Study:
- To determine if exercise-induced IL-6 is essential for full sympathoadrenal activation and immune cell mobilization during high-intensity exercise in humans.
- To investigate the impact of IL-6 receptor blockade on metabolic and hormonal responses to exercise.
Main Methods:
- Healthy young men underwent high-intensity interval exercise after receiving the IL-6 receptor (IL-6R) antibody, tocilizumab.
- Measurements included circulating epinephrine, plasma glucose, lactate, blood pH, and immune cell populations.
- Hypothalamic-pituitary-adrenal (HPA)-axis hormones were also assessed.
Main Results:
- IL-6R blockade significantly reduced epinephrine levels by approximately 50%, lowered plasma glucose, and attenuated lactate accumulation, leading to a less acidic blood pH.
- Immune cell mobilization was impaired, with reduced recruitment of lymphocytes, CD8+ T cells, certain NK cells, monocytes, neutrophils, and dendritic cells.
- Adrenocorticotropic hormone (ACTH) levels were reduced, correlating with pH and catecholamine responses.
Conclusions:
- IL-6 functions as an integrative metabolic signal that enhances organ crosstalk and amplifies the HPA and sympathoadrenal responses during high-intensity exercise.
- By connecting skeletal muscle metabolic stress to endocrine activation, glucose regulation, and immune cell mobilization, IL-6 coordinates the systemic fight-or-flight response.
- These findings elucidate IL-6's critical role in mediating the body's adaptation to intense physical exertion.
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