Do Acute Exercise-Induced Activations of the Kynurenine Pathway Induce Regulatory T-Cells on the Long-Term? - A Theoretical Frame Work Supported by Pilot Data

Regular physical activity and exercise interventions are suspected to have anti-inflammatory effects depending on exercise modality, thereby potentially reducing the risk and progress of several chronic diseases. Alterations in the kynurenine pathway may represent a link between inflammatory responses following acute exercise and chronic anti-inflammatory properties, such as increased levels of regulatory T-cells (T(reg)). Here, we hypothesize that acute exercise activates the kynurenine pathway and physical fitness is associated with proportions of circulating anti-inflammatory T(reg) in older healthy women. Nineteen older healthy female participants (55 years (SD: ± 5.6)) completed a cardiopulmonary incremental exercise test (CPET) with spirometry on a bicycle ergometer until exhaustion with maximum oxygen uptake (VO(2)max) as outcome. Blood samples were taken before (T0) and one minute after (T1) the CPET. Levels of tryptophan, serotonin and kynurenine were determined by enzyme-linked immunosorbent assays. Flow cytometry was used to identify proportions of T-cell subsets. Both, kynurenine (p = 0.003, d = 0.40) and the kynurenine/tryptophan ratio (p = 0.034, d = 0.48) increased significantly after acute exercise. Moreover, participants` VO(2)max was strongly correlated with T(reg) levels (p < 0.001, r = 0.689). This is the first study indicating a kynurenine pathway activation following acute exercise in older healthy women. The observed correlation between T(reg) levels and VO(2)max emphasizes a potential link between short-term upregulated kynurenine levels and longer-term anti-inflammatory properties of exercise. Future research is needed to clarify to what extend acute exercise-induced activations of the kynurenine pathway contribute to T(reg) differentiation.