Increased Endogenous Interleukin-1 Receptor Antagonist Levels after High Intensity Exercise in Healthy Adults

Introduction: Exercise triggers an inflammatory response in healthy adults which is followed by an anti-inflammatory response, including an increase in circulating levels of IL-1 receptor antagonist (IL-1Ra). Determining an optimal exercise prescription that can increase IL-1Ra and subsequently decrease inflammation may have therapeutic implications. Hypothesis: We hypothesized that calorically-equivalent high-intensity exercise (HIE) will induce a greater IL-1Ra response than moderate-intensity exercise (MIE). Aims: We aim to compare the changes in circulating IL-1Ra levels after moderate versus high-intensity exercise. Methods: Participants aged 18-55 years with a BMI between 18-40 kg/m 2 , without any known cardiovascular or rheumatologic disorders were included. Subjects underwent a standardized cycle ergometer protocol to measure lactate threshold (LT) and peak oxygen consumption (pVO 2 ) before three experimental visits in a random order: 1) control (CON); 2) HIE (75% delta between LT and pVO 2 ); and 3) MIE (at LT). Exercise was matched for energy expenditure within subjects. Venous blood was drawn pre-exercise/control, and every 30 minutes up to 180 min. Plasma IL-1Ra was measured using enzyme-linked immunosorbent assay (ELISA). Data are median [IQR] and compared between intensities using mixed models, with change over time (delta) compared using Wilcoxon signed-rank test. Results: We studied 14 adults (36 [26-45] years, 43% female, 64% white, BMI 33 [23-36], pVO 2 23.7 [19.8-34.5] ml/kg/min and 90 [77-102] % of predicted pVO 2 based on the Wasserman/Hansen formula). Baseline IL-1Ra levels were similar each visit ( p = 0.83). Energy expenditure was well-matched between intensities (HIE 272 [200 - 286] kcal, MIE 255 [197-292] kcal, p = 0.99). IL-1Ra was significantly different across exercise intensity ( p = 0.02), and time ( p = 0.03), with a trend for an interaction ( p = 0.06). Delta IL-1Ra at 180min was not significantly different during CON ( p = 0.54) or MIE ( p = 0.28), but was significantly higher after HIE ( p = 0.002). Conclusion: The anti-inflammatory cytokine IL-1Ra is increased after an individualized high intensity exercise bout, but not after moderate intensity exercise matched for energy expenditure. National Institute of Diabetes and Digestive and Kidney Diseases (5R01DK129510-02). This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.