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The aim of the study is to investigate the role of exercise-induced IL-6 in regulating energy stores and energy metabolism during recovery after an acute exercise bout. To achieve this, 30 men will be randomized to infusion placebo or tocilizumab (IL-6 receptor antibody) combined with a 2-hour exercise bout. Stable isotope tracers will be infused to determine substrate kinetics. Indirect calorimetry will be applied to determine substrate oxidation, and muscle biopsies will be taken to determine substrate uptake and storage.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Tocilizumab | Experimental | Participants will receive one 30 min intravenous infusion of tocilizumab/Actemra® (Roche). The dose will be 8 mg/kg bodyweight or a maximum of 800mg. Tocilizumab is dissolved in 100 mL 0.9% saline. |
|
| Saline | Placebo Comparator | As placebo, participants will receive one 30 min intravenous infusion of 100 mL 0.9% saline. |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Tocilizumab/Actemra® (Roche) | Drug | The infusion of tocilizumab will antagonize IL-6 signaling for the duration of the study, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise |
| Measure | Description | Time Frame |
|---|---|---|
| Change in muscle glycogen content (mmol/kg/h) | Comparing change in muscle glycogen in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery | Measured at 0, 120, 180 and 360 minutes |
| Change in muscle triglycerides content | Comparing change in muscle triglycerides in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery | Measured at 0, 120, 180 and 360 minutes |
| Change in muscle expression of glucose transporter type 4 (GLUT4) | Comparing muscle expression of GLUT4 before and immediately after exercise and 4 hours after recovery in the two groups | Measured at 0, 120 and 360 min |
| Change in muscle expression of fatty acid translocase (FAT/CD36) | Comparing muscle expression of FAT/CD36 before and immediately after exercise and 4 hours after recovery in the two groups | Measured at 0, 120 and 360 min |
| Change in muscle expression of muscle fatty acid binding protein (FABPm) | Comparing muscle expression of FABPm before and immediately after exercise and 4 hours after recovery in the two groups | Measured at 0, 120 and 360 min |
| Change in muscle expression of fatty acid transporter 4 (FATP4) | Comparing muscle expression of FATP4 before and immediately after exercise and 4 hours after recovery in the two groups | Measured at 0, 120 and 360 min |
| Measure | Description | Time Frame |
|---|---|---|
| Change in glucose rate of appearance | Comparing glucose rate of appearance during exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in glucose rate of disappearance |
| Measure | Description | Time Frame |
|---|---|---|
| Change in muscle total antioxidant capacity (TAC) | Comparing muscle total antioxidant capacity (TAC) at rest, after exercise and recovery in the two groups | Measured in muscle biopsies taken at 0, 120 and 360 minutes |
| Change in muscle superoxide levels (SOD) |
Inclusion Criteria:
Physically active (defined as meeting the ACSM's guidelines of 2.5h per week of moderate to vigorous physical activity per week), young, healthy males will be included. Participants may be included in the study if they meet all the following criteria:
Exclusion Criteria:
• Cardiovascular disease
Eligibility is NOT based on self-representation of gender identity
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| Name | Affiliation | Role |
|---|---|---|
| Bente K Pedersen, MD | Rigshospitalet, Denmark | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Centre for Physical Activity Research, Rigshospitalet Section 7641 | Copenhagen | Capital Region | 2100 | Denmark |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 41242537 | Derived | Kistner TM, Trinh B, Mfeketo K, van Hall G, Pedersen BK, Lieberman DE, Ellingsgaard H. Myokine IL-6 activity enhances post-exercise fatty acid accumulation in skeletal muscle but does not affect glycogen resynthesis. Mol Metab. 2026 Jan;103:102283. doi: 10.1016/j.molmet.2025.102283. Epub 2025 Nov 14. |
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| ID | Term |
|---|---|
| C502936 | tocilizumab |
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Randomized, placebo-controlled, double-blind
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Participants and investigators will be blinded to the infusion of saline or tocilizumab
| Saline 9% | Drug | The infusion of saline will serve as placebo for tocilizumab, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise |
|
| Change in muscle expression of glycerol transporters | Comparing muscle expression of glycerol transporters before and immediately after exercise and 4 hours after recovery in the two groups | Measured at 0, 120 and 360 min |
Comparing glucose rate of disappearance during exercise and recovery in the two groups |
| Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in glucose concentration | Comparing glucose concentration during exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in glucose enrichment in intramuscular glycogen | Comparing glucose enrichment in intramuscular glycogen during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in intramuscular glucose concentration | Comparing intramuscular glucose concentration during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in glycogen fractional synthesis rate | Comparing intramuscular glycogen fractional synthesis rate during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in gylcerol rate of appearance | Comparing gylcerol rate of appearance during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in gylcerol rate of disappearance | Comparing gylcerol rate of disappearance during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in gylcerol concentration | Comparing gylcerol concentration during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in palmitate rate of appearance | Comparing palmitate rate of appearance during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in palmitate rate of disappearance | Comparing palmitate rate of disappearance during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in palmitate concentration | Comparing palmitate kinetics during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in palmitate oxidation | Comparing palmitate oxidation during rest, exercise and recovery in the two groups | Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in intramuscular palmitate content | Comparing intramuscular palmitate content during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in palmitate enrichment in intramuscular triglycerides | Comparing palmitate enrichment in intramuscular triglycerides during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in intramuscular triglycerides fractional synthesis rate | Comparing intramuscular triglycerides fractional synthesis rate during rest, exercise and recovery in the two groups | Measured at 0, 120, 180 and 360 minutes |
| Change in haemoglobin | Comparing haemoglobin during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in haematocrit | Comparing haematocrit during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in differential blood count | Comparing differential blood count during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-6 concentration | Comparing plasma IL-6 concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma TNF-alpha concentration | Comparing plasma TNF-alpha concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-8 concentration | Comparing plasma IL-8 concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-10 concentration | Comparing plasma IL-10 concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-1beta concentration | Comparing plasma IL-1beta concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-1Ra concentration | Comparing plasma IL-1Ra concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma IL-4 concentration | Comparing plasma IL-4 concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in plasma sIL-6R concentration | Comparing plasma sIL-6R concentration during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in insulin | Comparing insulin during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in c-peptide | Comparing c-peptide during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in glucagon | Comparing glucagon during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in growth hormone (GH) | Comparing GH during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in adrenaline | Comparing adrenaline during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in noradrenaline | Comparing noradrenaline during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in cortisol | Comparing cortisol during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in total glucagon-like peptide-1 (GLP-1) | Comparing total GLP-1 during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in active GLP-1 | Comparing active GLP-1 during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in gastric inhibitory peptide (GIP) | Comparing GIP during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in peptide YY (PYY) | Comparing PYY during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in leptin | Comparing leptin during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
| Change in triglycerides | Comparing triglycerides during rest, exercise and recovery in the two groups | Measured at -150, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes |
Comparing muscle superoxide levels (SOD) at rest, after exercise and recovery in the two groups
| Measured in muscle biopsies taken at 0, 120 and 360 minutes |
| Excess post-exercise oxygen consumption | Comparing excess post-exercise oxygen consumption between the two groups | Measured at -130, 0, 60, 120, 180, 240, 300 and 360 minutes |