Sex-specific cytokine and signaling responses to acute high-intensity interval exercise in recreationally active young adults.

High-intensity interval exercise (HIIE) induces transient increases in reactive oxygen species (ROS) and inflammatory mediators that drive skeletal muscle adaptations. Sex influences oxidative stress and inflammation, yet the interplay between sex and exercise-induced signaling remains incompletely understood. The purpose of this study was to investigate sex differences in markers of inflammation, oxidative stress, and antioxidant status at rest and following acute HIIE in young, healthy males and females matched for aerobic fitness. Twenty-four participants (12/sex) underwent muscle biopsies and blood sampling at rest and immediately postexercise (10 × 1 min at 90% HRmax). Skeletal muscle was analyzed for oxidative stress [NADPH oxidase 2 (NOX2), 4-hydroxynonenal (4HNE), total protein carbonylation via oxyblot, p38 MAPK], antioxidant enzymes [thioredoxin 1 (TRX1), glutathione reductase (GR), and glutathione peroxidase 1 (GPX1)], and cytokine content (array), and plasma was analyzed for inflammatory markers (IL-6 and TNFα) and antioxidant status. Acute HIIE increased plasma IL-6 and TNFα and decreased total antioxidant status with no differences between sexes. Basally, females had higher phosphorylation of p38 MAPK and elevated growth- and repair-associated cytokines [insulin-like growth factor binding protein 1 and 3 (IGFBP-1/3), tissue inhibitors of metalloproteinases 1 and 2 (TIMP-1/2), transforming growth factor- β2/3 (TGF-β2/3), FGF-7/9, macrophage colony-stimulating factor (M-CSF), and stromal cell derived factor (SDF)-1], whereas males had higher basal proinflammatory cytokines (IL-1α, IL-13, IP-10, and oncostatin M). Following exercise, males showed a greater upregulation of growth and repair mediators, whereas females had broader suppression of inflammatory and chemotactic factors. No sex differences were observed in muscle oxidative stress markers or antioxidant content. These findings indicate that although acute HIIE elicits comparable plasma inflammatory responses in males and females, underlying skeletal muscle cytokine signaling and adaptive potential are sex-specific, emphasizing the need to consider sex in exercise physiology studies. NEW & NOTEWORTHY We investigated whether sex influenced the inflammatory or oxidative stress response to acute exercise. Although no differences were observed in plasma markers, in skeletal muscle, females had elevated growth- and repair-associated cytokines, whereas males had higher proinflammatory cytokines at rest. Following exercise, males had greater upregulation of growth and repair mediators, whereas inflammatory and chemotactic factors were suppressed in females. The sex divergence in skeletal muscle cytokines may have implications postexercise signaling and chronic adaptations.