Circulating Myokine Responses to Acute Endurance Exercise and Their Role in Immunoregulation: A Systematic Review and Meta‐Analysis

Acute endurance exercise influences metabolic and immune functions, with myokines playing a key role in mediating communication between these two systems and in transforming transient inflammatory signals into long-term anti-inflammatory adaptations. However, the magnitude of these anti-inflammatory effects varies widely depending on exercise type, intensity, and duration. Accordingly, the objective of this meta-analysis is to assess changes in myokine concentrations following endurance exercise and establish a potential dose-response relationship between exercise-related parameters. A systematic literature search was conducted in June 2024 for endurance exercise studies measuring changes in interleukin (IL-) 6, IL-10, IL-1ra, tumor necrosis factor (TNF-) α, IL-15, IL-7, IL-8, transforming growth factor β1, and fractalkines before and immediately after exercise in healthy individuals. Independent random-effect meta-analyses were performed for each myokine (PROSPERO: CRD42024535364). Significant small-moderate to very large positive effect sizes were observed for IL-6, IL-10, IL-1ra, IL-8, IL-15, and TNF-α. These effects were significantly moderated by risk of bias, sex, age, V̇O₂peak, experience, exercise type, intensity, duration, dose, sample, fasting state, and time of day. This meta-analysis demonstrates that myokine responses following endurance exercise are clearly increased and moderated by factors such as exercise duration, intensity, exercise type, and training status, allowing their targeted modulation for therapeutic use. Even "suboptimal exercise conditions" can elicit significant increases in immunoregulatory myokines, thereby promoting beneficial immune responses, suggesting that endurance exercise is a key component in the treatment of a wide range of diseases.