Short-Lived Exercise-Induced Exerkines Modulate Inflammation for Chronic Disease Prevention: A Systematic Review and Meta-Analysis

Physical exercise triggers the release of short-lived exerkines, such as interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-α), and interleukin-10 (IL-10), which may help reduce systemic inflammation and mitigate the risk of chronic disease. Despite their potential, the effects of these exercise-induced cytokines (termed exerkines) across diverse populations remain underexplored. This study evaluated how exercise-induced exerkines modulate inflammatory markers, based on changes observed before and after intervention. We systematically searched PubMed, Scopus, and Web of Science from January 2015 up to 7 February 2025, identifying 11 randomized controlled trials (RCTs) involving 1135 participants. Standardized mean differences (SMDs) with 95% confidence intervals (CIs) were calculated using a random-effects model to assess changes in IL-6, TNF-α, IL-10, C-reactive protein (CRP), and interferon-gamma (IFN-γ). Study quality was evaluated using the Cochrane Risk of Bias 2 tool. Exercise significantly reduced CRP (SMD = −0.77, 95% CI: −1.20 to −0.33, p = 0.001) and TNF-α (SMD = −1.09, 95% CI: −2.14 to −0.03, p = 0.043) while increasing IL-6 (SMD = 0.81, 95% CI: 0.10 to 1.53, p = 0.026). IL-10 showed a non-significant increase (SMD = 0.66, 95% CI: −0.09 to 1.41, p = 0.084), with no effect on IFN-γ. Heterogeneity was moderate for CRP (I2 = 52.5%) but high for other markers (I2 > 87%). These findings suggest that exerkines contribute to an anti-inflammatory shift in the short term, which is consistent with mechanisms that may underlie the preventive effects of exercise against cardiometabolic diseases; however, standardized protocols and longitudinal studies with clinical endpoints are needed to confirm any long-term benefits.