There is a strong rationale suggesting that the observed initial activation of the KYN pathway as well as the increase in the metabolic flux towards QA is driven by immune activation as they appear transiently during and after single bouts of exercise. Immune activation during and after acute exercise has especially been described as an elevation in inflammatory cytokines such as interleukin-6 (IL-6).24,25 Indeed, primarily interferon-γ (IFN-γ) and also other inflammatory cytokines (eg, IL-6) are known to induce IDO1, IDO2, and KMO,5 thereby creating a solid link to an IDO-mediated upregulation of the KYN pathway and an increased degradation of KYN to QA in response to acute exercise. However, this hypothesis has not yet been investigated in detail and needs to be addressed in future research.