Your muscles are chattier than you might think. During exercise, they release chemical messengers called myokines that circulate through your bloodstream and influence everything from immune function to brain health. These aren’t just byproducts of movement. They’re a sophisticated signalling system that your body has been refining for millennia.
What is a myokine
A myokine is a protein released by muscle tissue during contraction. Think of it as a molecular text message sent from your muscles to distant organs. The name itself gives away the mechanism: myo for muscle, kine for movement or signalling. When muscle fibres contract, they don’t just burn fuel and generate force. They produce and secrete dozens of different proteins that act on the liver, brain, adipose tissue, and immune cells.
Interleukin-6, or IL-6, is perhaps the most studied myokine. During exercise, muscle tissue can increase IL-6 production a hundred fold or more. Yet here’s where it gets interesting: IL-6 from exercise works differently than IL-6 released during inflammation or infection. The same molecule, different context, vastly different effects on your cells.
Other myokines get less attention but matter just as much. Irisin, IL-15, and myostatin influence muscle growth, fat metabolism, and bone density. Each one carries information about what your muscles are currently doing, allowing your body to coordinate a response across multiple systems.
What the research shows
Scientists have observed that exercise triggers a coordinated release of myokines within minutes of muscle contraction. IL-6 levels rise sharply during and immediately after activity, then taper back down. The magnitude of the response depends on exercise intensity, duration, and your current fitness level.
What researchers found particularly interesting is that trained athletes produce different myokine profiles than untrained individuals doing the same workout. A person who trains regularly shows a blunted IL-6 response to moderate exercise but can still mount a vigorous response to high intensity effort. This adaptation suggests the body learns to manage its signalling more efficiently with repeated training.
Animal studies have demonstrated that myokines can cross the blood-brain barrier and influence neuroinflammation. IL-6 produced during exercise appears to reduce pro-inflammatory markers in the brain itself. In liver tissue, exercise-induced myokines prompt changes in glucose metabolism and insulin sensitivity. Bone cells respond to myokine signalling by increasing turnover and density.
The immune system shows particularly clear responses. IL-6 from exercise stimulates the production of anti-inflammatory cytokines like IL-10. It triggers the release of immune cells into the bloodstream. Yet the effect is temporary and recovery focused, not the prolonged immune activation seen in chronic inflammation.
Why cells need this
From an evolutionary standpoint, myokines solve a timing problem. When your muscles contract, they create local demands: damaged proteins need clearing, fuel needs replenishing, tissue needs remodelling. But your liver needs to know to release more glucose. Your brain needs to know you’re active so it can adjust arousal and cognition. Your immune system needs coordination signals so it fixes problems without overreacting.
Exercise is fundamentally a stressor. Myokines let your muscles communicate with the rest of your body about what kind of stress is happening and what response is needed. This is protective signalling, not an alarm. Your immune system gets instructed to clear debris and consolidate gains rather than mount a defensive attack.
IL-6 specifically serves as a metabolic switch. Its presence tells other tissues that energy demand is high and metabolic adjustment is required. Without this signal, your body can’t optimise its response to training. The adaptation that follows exercise, whether that’s improved endurance or increased strength, depends partly on these myokine messages reaching the right cells at the right time.
What affects myokine production
Exercise intensity matters enormously. Low intensity movement produces modest myokine responses. High intensity efforts, or resistance training that creates significant muscle damage, trigger robust myokine release. Interval training consistently produces strong signalling responses even with shorter duration.
Your fitness level shapes the picture too. Untrained individuals show larger absolute increases in IL-6 during moderate exercise. Trained athletes show more nuanced responses, with lower basal levels but the capacity for high production during intense efforts. This adaptation happens within weeks of regular training.
Age appears to blunt myokine responses. Older adults often produce lower levels of IL-6 and other myokines in response to the same exercise stimulus that produces robust responses in younger people. Some researchers propose this contributes to the reduced adaptability of ageing muscle. Whether this is cause or consequence remains unclear.
Nutrition state influences myokine production. Training in a fed state versus fasted state produces different myokine profiles. Recovery status matters too. Well rested individuals show different responses than fatigued ones doing identical exercise. Chronic sleep deprivation appears to alter baseline myokine levels and exercise responses.
What remains unknown
The precise targets of different myokines remain incompletely mapped. Researchers know IL-6 acts on liver, muscle, and brain tissue, but the full scope of responsive cell types and the specific outcomes of signalling in each location are still being discovered. New myokines get identified regularly, suggesting the full complement of exercise signalling molecules hasn’t been catalogued yet.
The relationship between acute myokine responses and long term adaptation is still murky. Does the magnitude of IL-6 spike predict how much muscle growth will follow? Does blunted myokine response in older adults explain reduced training adaptability, or is myokine response merely a marker of something else? Scientists are actively working these questions but lack clear answers.
The optimal dose remains undefined. More intense exercise produces larger myokine responses, but is there a plateau? Is there a point where additional signalling stops producing additional benefit? Different types of training produce different myokine signatures. Which signature is most beneficial for specific outcomes remains an open question.
Individual variation is substantial but largely unexplained. Two people of similar age and fitness doing identical exercise produce different myokine responses. Genetic factors clearly play a role, but which genes matter most and why they differ between people is still being investigated.
Myokines represent a reminder that exercise isn’t just about muscles contracting. It’s a full body conversation conducted through chemical messengers, with muscles providing information that every other organ system needs to hear. Understanding this signalling network helps explain why regular movement influences health across multiple domains, from metabolic control to brain function to immune resilience. The more researchers investigate how muscles communicate, the clearer it becomes that movement is fundamentally a systems phenomenon, coordinated by molecules that muscles release when they’re asked to work.
Matt Elliott is the editor of Redox News Today, an independent publication covering peer-reviewed research on cellular health, redox signalling, and related biomedical science.
