Intensity- and time-matched acute interval and continuous endurance exercise similarly induce an anti-inflammatory environment in recreationally active runners: focus on PD-1 expression in Tregs and the IL-6/IL-10 axis

Abstract

Purpose: Acute exercise elicits a transient anti-inflammatory state during the early recovery period. Since recent studies reported on regimen-specific effects on immune-related humoral factors and cellular subsets, this study compared the effects of intensity- and time-matched acute interval and continuous exercise on peripheral anti-inflammatory cellular and humoral immune parameters with a particular focus on the PD-1 expression in CD4⁺ regulatory T cells (T_regs).

Methods: Twenty-four recreationally active runners (age: 29.7 ± 4.3 years, BMI: 22.2 ± 2.4, VO_2peak: 56.6 ± 6.4 ml × kg^-1 × min^-1) participated in this crossover RCT. Each subject conducted a moderate continuous (MCE) and a high-intensity interval exercise (HIIE) session in a counterbalanced design. Blood was drawn before, immediately after, and 1 h after exercise. T_reg subsets and levels of PD-1 and Foxp3 were assessed by flow cytometry. Serum levels of IL-10 and IL-6 were quantified by ELISA.

Results: PD-1 levels on T_regs increased within the recovery period after HIIE (p < .001) and MCE (p < 0.001). Total counts of T_regs (HIIE: p = 0.044; MCE: p = .021), naïve T_regs (HIIE: p < 0.001; MCE: p < 0.001), and PD-1⁺ effector T_regs (eT_regs) (HIIE: p = .002) decreased 1 h after exercise. IL-10 increased 1 h after HIIE (p < 0.001) and MCE (p = 0.018), while IL-6 increased immediately after both HIIE (p = 0.031) and MCE (p = 0.021). Correlations between changes in IL-6 and IL-10 (p = 0.017, r = 0.379) and baseline VO_2peak and T_reg frequency (p = 0.002, r = 0.660) were identified.

Conclusion: This is the first study that investigates PD-1 expression in circulating T_regs after acute exercise, revealing an increase in PD-1 levels on eT_regs during the early recovery period after intensity- and time-matched HIIE and MCE. Future studies are needed to investigate the PD-1 signalosome in eT_regs, together with the expression of key effector molecules (i.e., IL-10, TGF-β, IL-35, CTLA-4) to elucidate PD-1-dependent changes in cellular function. Based on changes in serum cytokines, this study further reveals a regimen-independent establishment of an anti-inflammatory milieu and underpins the role of the IL-6/IL-10 axis.

Keywords: Cytokines; HIIT; PD-1; Regulatory T cells.