Background: Repeated sprint exercise (RSE) induces inflammation, which may be modulated by fat-free mass (FFM), biological maturation (BM), and dietary patterns, assessed by the Dietary Inflammatory Index (DII). Aim: To examine the influences of FFM, BM, and DII on cytokine responses to RSE in male athletes. Methods: A study with a quasi-experimental approach and cross-sectional design with a sample of 30 male athletes (20-adolescents, 10-adults). Blood samples were collected pre-, immediately after, 2 h and 24 h after RSE (3-sets of 6 × 35-m sprints). IL-1ß, IL-6, IL-8, and IL-10 were analyzed via flow cytometry. FFM was assessed by DXA, BM by predictive models, and DII by 24 h dietary recalls. Prior exploratory analyses included Spearman's and partial correlations, and Mann-Whitney-U-tests. Main analyses were conducted using Generalized-Linear-Mixed-Models (GLMM). Results: The GLMMs confirmed that BM, FFM, and DII significantly influenced cytokine responses (p < 0.05). FFM emerged as a significant predictor of IL-1ß (p = 0.0023). For IL-6, there was a time effect (p < 0.001) and a Time × BM interaction (p = 0.040), with FFM and DII being significant predictors in both groups. A similar interaction was observed for IL-8 (p = 0.036). For IL-10, there was a Time × BM interaction (p < 0.001), where adults showed superiority over adolescents (p < 0.05). Post hoc analyses revealed that adolescents with lower FFM had a more prolonged inflammatory response (increased-IL-6), while adults with higher FFM demonstrated a more effective anti-inflammatory capacity (increased-IL-10). Conclusion: FFM, BM, and DII play key roles in shaping the inflammatory response to RSE and should be considered when prescribing training loads to optimize recovery and performance.
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