The exploration of immune system function changes in marathon athletes after high-intensity training by Agent-Based Model

Background Marathon running imposes substantial metabolic demand. While the acute effects of exercise are well-documented, the chronic immunometabolic alterations associated with intensified training blocks in elite populations remain characterized by complex, non-linear dynamics. Contemporary debates persist regarding whether post-exercise lymphopenia represents immunosuppression (the “open window”) or a functional redistribution of immune effectors. This study explored the chronic effects of a four-week high-intensity training (HIT) block on immune markers in professional marathon athletes and evaluated the utility of an Agent-Based Model (ABM) for visualizing these system behaviors. Methods Twenty-two professional marathon athletes (14 male, 8 female) underwent a four-week intensified training protocol characterized by sustained time in the severe-intensity domain (blood lactate > 7.0 mmol/L). Peripheral blood samples were analyzed pre- and post-training for leukocytes, immunoglobulins (Ig), cytokines (IL-6, IL-8, IL-10, TNF-α), and lymphocyte subsets. Concurrently, a NetLogo-based ABM was developed to simulate theoretical immune system dynamics under metabolic constraints. Results The training period coincided with significant shifts in circulating immune markers. Total leukocyte counts and serum IgG levels were significantly lower post-training ( P < 0.01). A marked inversion in T-cell homeostasis was observed, with the CD4+/CD8+ ratio decreasing to 0.98 ( P < 0.01), driven by a reduction in CD4+ cells and maintenance of CD8+ populations. Cytokine analysis revealed a “resolution failure” profile: while pro-inflammatory markers IL-6, IL-8, and TNF-α increased ( P < 0.01), the anti-inflammatory cytokine IL-10 was significantly reduced ( P < 0.001). The ABM simulation qualitatively reproduced these emergent patterns, visualizing the non-linear contraction of T-cell populations consistent with the empirical data. Conclusions A four-week block of high-intensity marathon training is associated with a state of immunometabolic perturbation characterized by reduced circulating leukocytes, CD4+/CD8+ imbalance, and an uncoupled inflammatory-resolution cytokine response. While plasma volume expansion may contribute to the observed lower cell concentrations, the specific suppression of IL-10 and CD4+ cells suggests a maladaptive response to chronic load. The agent-based model serves as an exploratory tool for visualizing potential immunological tipping points during intensified training, bridging the gap between reductionist data and complex system dynamics

Athletes · Cytokine · Elite Athletes · Homeostasis · Immune system · Immunosuppression · Lymphocyte · Exercise and Physiological Responses · High Altitude and Hypoxia · Immunotoxicology and immune responses

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