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IL-6 release from muscles during exercise is stimulated by lactate-dependent protease activity
Pernille Hojman1, Camilla Brolin2, Nynne Nørgaard-Christensen1
1Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Copenhagen University Hospital, University of Copenhagen , Copenhagen , Denmark.
American Journal of Physiology. Endocrinology and Metabolism
|February 20, 2019
Summary
Exercise intensity drives the release of interleukin-6 (IL-6) from muscles. Lactate production activates proteases, releasing IL-6 stored in muscle vesicles during strenuous physical activity.
Area of Science:
- Exercise Physiology
- Molecular Biology
- Endocrinology
Background:
- Interleukin-6 (IL-6) is released from muscles during exercise, acting as an energy sensor.
- Muscle-derived IL-6 influences energy substrate release from the liver and adipose tissues.
Purpose of the Study:
- To investigate the mechanism behind exercise-induced IL-6 surges.
- To explore the role of lactate production in muscular IL-6 release during exercise.
Main Methods:
- Utilized interval cycling in humans, swimming in mice, and electrical stimulation of human muscle cells.
- Employed in vivo bioimaging and protease activity blockade in mice.
- Administered intramuscular lactate and hyaluronidase injections in mice.
Main Results:
- Observed a strong correlation between lactate production and IL-6 release.
- Demonstrated that lactate injection mimicked exercise-induced IL-6 release.
- Identified protease activation and IL-6-containing vesicle release from muscle fibers.
Conclusions:
- Lactate production initiates protease-dependent IL-6 release from skeletal muscle vesicles.
- This mechanism links exercise intensity and lactate production to IL-6 secretion during strenuous exercise.
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