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.

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