title: Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study.
abstract: Exercise increases muscle derived Interleukin–6 (IL–6) leading to insulin secretion via glucagon-like peptide–1. IL–1 antagonism improves glycemia and decreases systemic inflammation including IL–6 in patients with type 2 diabetes. However, it is not known whether physiological, exercise-induced muscle-derived IL–6 is also regulated by the IL–1 system. Therefore we conducted a double blind, crossover study in 17 healthy male subjects randomized to receive either the IL–1 receptor antagonist IL-1Ra (anakinra) or placebo prior to an acute treadmill exercise. Muscle activity led to a 2–3 fold increase in serum IL–6 concentrations but anakinra had no effect on this exercise-induced IL–6. Furthermore, the IL–1 responsive inflammatory markers CRP, cortisol and MCP–1 remained largely unaffected by exercise and anakinra. We conclude that the beneficial effect of muscle-induced IL–6 is not meaningfully affected by IL–1 antagonism.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01771445.
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department Biomedicine. University of Basel, 4031 Basel, Switzerland.
authors.forename: Thierry M
authors.initials: TM
authors.lastname: Nordmann
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department Biomedicine. University of Basel, 4031 Basel, Switzerland.
authors.forename: Eleonora
authors.initials: E
authors.lastname: Seelig
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department Biomedicine. University of Basel, 4031 Basel, Switzerland.
authors.forename: Katharina
authors.initials: K
authors.lastname: Timper
authors.affiliation: Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.
authors.forename: Mareike
authors.initials: M
authors.lastname: Cordes
authors.affiliation: Clinical Trial Unit, University Hospital Basel, 4031 Basel, Switzerland.
authors.forename: Michael
authors.initials: M
authors.lastname: Coslovsky
authors.affiliation: Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.
authors.forename: Henner
authors.initials: H
authors.lastname: Hanssen
authors.affiliation: Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.
authors.forename: Arno
authors.initials: A
authors.lastname: Schmidt-Trucksäss
authors.affiliation: Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department Biomedicine. University of Basel, 4031 Basel, Switzerland.
authors.forename: Marc Y
authors.initials: MY
authors.lastname: Donath
mesh_terms: D000328:Adult; D002097:C-Reactive Protein / Q000032:analysis; D002460:Cell Line; D018925:Chemokines / Q000378:metabolism; D018592:Cross-Over Studies; D003924:Diabetes Mellitus, Type 2 / Q000097:blood / Q000378:metabolism / Q000473:pathology; D004311:Double-Blind Method; D015444:Exercise; D006801:Humans; D050417:Insulin-Secreting Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015850:Interleukin-6 / Q000097:blood*; D016209:Interleukin-8 / Q000097:blood; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000378:metabolism*; D015990:Placebo Effect; D017472:Receptors, Interleukin-1 / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000494:pharmacology; D044967:Serum / Q000737:chemistry
chemical_list: D018925:Chemokines; D053583:Interleukin-1beta; D015850:Interleukin-6; D016209:Interleukin-8; D017472:Receptors, Interleukin-1; D011994:Recombinant Proteins; D002097:C-Reactive Protein