Serum cytokines and their soluble receptors are differently regulated between trained and untrained men after vigorous endurance exercise

Endurance training contributes to immune system changes that help manage exercise-induced stress and promote an anti-inflammatory effect. However, the specific mechanisms underlying these adaptations are still being explored. Cytokines play a key role in both acute and chronic exercise responses through interactions with their receptors, which are present in both membrane-bound and soluble forms. Yet, the impact of exercise on cytokines and soluble cytokine receptors in parallel remains understudied. Therefore, the purpose of this study was to assess how cytokines and their soluble receptors change in serum after vigorous exercise in endurance-trained and untrained men. Following 1-h of cycling at their respiratory compensation point, untrained men (<i>n</i> = 5) exhibited a significant increase in proinflammatory cytokines, including IL-6, TNF-α, IL-1β, CCL2, and VEGFA. In contrast, anti-inflammatory cytokines such as IL-10 and IL-1Ra were reduced. These effects were not observed in the trained group (<i>n</i> = 7). Instead, proinflammatory cytokine levels remained close to the baseline, whereas the anti-inflammatory cytokines IL-10 and IL-1Ra increased. In the trained group, these cytokine changes were accompanied by a marked increase in the expression of soluble cytokine receptors known to inhibit cytokine-mediated signaling, such as sIL-1RII, sGP130, sTNFRI, sTNFRII, sVEGFR1, and sVEGFR2, indicating reduced cytokine bioavailability. However, in the untrained group, the expression of these soluble cytokine receptors either remained unchanged or decreased, suggesting greater cytokine bioavailability. Together these findings highlight a novel potential anti-inflammatory adaptation such that trained men present a blunted inflammatory response by both reduced inflammatory cytokines and increased soluble cytokine receptors after exercise compared with untrained men.<b>NEW & NOTEWORTHY</b> Our study identifies a novel potential anti-inflammatory adaptation to endurance training, where trained men present a blunted inflammatory response characterized by reduced inflammatory cytokines and increased soluble cytokine receptors, resulting in decreased cytokine bioavailability after exercise compared with untrained men.