type 1 interferon induced changes to exercise adaptations in systemic lupus erythematosus patients

Conditions: Systemic Lupus Erythematosus; Interferon Deficiency

Summary: investigating the physiological effects of the interferons type 1 and 2 (ifns), and the cytokines interleukin 6 (il-6) and tumor necrosis factor (tnf) on the adaptive changes to exercise in patients with systemic lupus erythematosus (sle). the investigators hypothesize that the pathogenic blockage of il-6 signalling that occurs in sle, will decrease the cardiac and metabolic adaptations to aerobic exercise, and this decrease can be related to the ifn signature. 55 patients was included in a 12-week investigator blinded 1:1 randomised high intensity aerobic exercise intervention study.

55 patients with sle have been included and randomized in a 1:1 fashion to a 12 week high intensity interval training (hiit) course or standard care. randomization was stratified by sex. all patients will undergo baseline and followup testing including: vo2max, pulmonary function, capillaroscopy, ogtt, blood tests, epigenetic markers of ifn, tnf and il-6 signalling, echocardiography,dxa, medical examination, acute exercise bout with blood tests during and after an exercise bout similar to the intervention. a subgroup of patients will be offered a 82-rb pet ct of the heart as opt-in. the exercise programme consists of 12 weeks of tri-weekly exercise bouts of 38-45 minutes, following warm-up subjects will undergo 4 sets of 4 minute high intensity exercise, measured as the pulse being above 85% of hrmax for more than half the time; and 3 minute low to medium intensity exercise between the high intensity sets, measured as the pulse being between 40 to 60% of hrmax.

Eligibility criteria:
inclusion criteria: * age ≥ 18 years by inclusion. * able to provide informed consent. * diagnosed sle and fulfilling the classification criteria for sle based on the american college of rheumatology/eular criteria (slicc) exclusion criteria: * health conditions that prevent participating in the exercise intervention determined by the research coordinator these include but are not limited to * major bone fracture at inclusion * significant myalgias exacerbated by physical exercise * active infectious disease such as covid-19 * severe symptomatic pleuritis or pericarditis * corticosteroid use \> 10mg/day at baseline * diagnosed with diabetes mellitus by physician * pregnancy * sledai-2k (with the selena modifications to proteinuria changes so as to not exclude patients with chronic proteinuria) \> 10 * contraindications to 82rb-pet with adenosine stress (according to local guidelines at the dept. of clinical physiology, nuclear medicine and pet, rigshospitalet, which are in accordance with the recommendations of the european association of nuclear medicine) * fever, myocarditis or endocarditis * previous heart transplantation * dysregulated atrial or ventricular tachyarrhythmias * severe chronic obstructive pulmonary disease with a fev1 of less than 50% of predicted * second or third degree sinoatrial or atrioventricular block * active bronchospasm at the time of the scan * systolic blood pressure \ 200 mmhg at the time of the scan * treatment with theophyllin within 7 days of the scan

Keywords: cardiac adaptations metabolic adaptations high intensity interval training interleukin-6 signature tumor necrosis factor signature interferon signature