Abstract and Introduction
Abstract
Context: One acute bout of exercise leads to a rapid increase in the systemic cytokine concentration. Regular exercise might alter the cytokine response, in particular in beforehand untrained and obese individuals.
Objective: Using a proximity extension assay, we studied the effects of acute exercise as well as endurance training on a panel of 92 cytokines related to inflammation.
Methods: A total of 22 individuals (30 ± 9 years; peak oxygen uptake [VO2peak] 25.2 ± 4.2 mL/[kg × min]; body mass index [BMI] 31.7 ± 4.4) participated in an 8-week endurance exercise intervention. Blood samples were collected before and immediately after 30 minutes' ergometer exercise at 80% VO2peak.
Results: Before and after the training intervention, 40 and 37 cytokines, respectively, were acutely increased more than 1.2-fold (Benjamini-Hochberg [BH]-adjusted P < .05). The exercise intervention did not change the acute increase in cytokines nor the resting cytokine levels, whereas fitness was improved and adiposity reduced. The increase in fitness led to a slight increase in power output when exercising at the same heart rate, which might explain the comparable increase in cytokines before and after the intervention. The largest acute increase was found for OSM, TGFA, CXCL1 and 5, and TNFSF14 (≥ 1.9-fold, BH-adjusted P < .001). The transcript levels of these proteins in whole blood were also elevated, particularly in the trained state. Only the acute increase in IL6 (1.3-fold) was related to the increase in lactate, confirming the lactate-driven secretion of IL6.
Conclusion: Our comprehensive proteomics approach detected several underexplored serum exerkines with up to now less understood function in the adaptation to exercise.
Introduction
The acute cytokine response to one single bout of exercise was first observed in 1983[1] in the form of pyrogenic activity of plasma obtained from humans after exercise. Later on, this effect on body temperature was attributed to the increase in plasma interleukin-6 (IL6), which was found to be released from the exercising leg.[2] This kicked off not only 1 but 2 emerging research fields. The first is the immunomodulatory function of exercise and its relevance in the prevention of chronic metabolic diseases[3] and of aging-associated disorders.[4] The second is the field of myokines and other exercise-induced secreted factors that support the functional adaptation of the organism to repeated bouts of exercise and contribute to the beneficial effect of regular physical activity on human health.[5] The enormous interest in this research area led to the discovery that several cytokines are elevated in the blood stream after one acute bout of exercise including the interleukins IL1β, IL4, IL13, IL8, IL10, and IL15, interleukin receptor antagonist IL1Ra, colony-stimulating factors, tumor necrosis factor (TNF), and chemokine ligands, such as CCL2 and CX3CL1.[6–8] The acute release of cytokines with mainly anti-inflammatory properties, such as IL10, IL1Ra, and IL6, is considered one of the potent mechanisms by which exercise modulates the function of monocytes and macrophages, directing them toward a less proinflammatory phenotype.[6] Notably, many cells are capable of producing cytokines. The systemic concentration always reflects the sum of the release from all sources minus the clearance rate. Measuring the arteriovenous difference over the exercising leg validated the release of some, but not all, cytokines showing increased systemic blood levels from skeletal muscle.[5] Other sources for cytokine release into the circulation in response to exercise are natural killer (NK) cells,[9] monocytes, macrophages, and T cells.[10]
Most previous studies have focused on small, predefined sets of cytokines rather than evaluating the broad cytokine response in an unbiased approach. Moreover, low physical fitness as well as an increased amount of visceral and subcutaneous fat, which harbors a relevant number of macrophages and T cells, might influence the cytokine pattern after acute exercise. Fitness and adiposity both are improved by endurance training, which might change the acute cytokine response. To address this question we made use of the recently developed proximity extension analysis, which allows the simultaneous measurement of a large number of inflammatory cytokines.[11] We applied this technique to blood samples collected before and 5 minutes after one 30-minute ergometer exercise bout at 80% peak oxygen uptake (VO2peak). The participants were middle-aged, untrained, and had overweight or obesity.[12] After the first exercise bout, they underwent an 8-week endurance exercise training with 3 60-minute sessions per week followed by the second 30-minute ergometer exercise bout with collection of blood samples. We investigated the acute regulation of a cytokine panel covering 92 analytes and assessed whether this response is altered after the 8-week training period. Furthermore, we analyzed the influence of fitness and metabolic parameters on the cytokine response.
J Clin Endocrinol Metab. 2023;108(4):865-875. © 2023 Endocrine Society