Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study

Thierry M Nordmann; Eleonora Seelig; Katharina Timper; Mareike Cordes; Michael Coslovsky; Henner Hanssen; Arno Schmidt-Trucksäss; Marc Y Donath

doi:10.1371/journal.pone.0139662

Muscle-Derived IL-6 Is Not Regulated by IL-1 during Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study

PLoS One. 2015 Oct 8;10(10):e0139662. doi: 10.1371/journal.pone.0139662. eCollection 2015.

Authors

Thierry M Nordmann¹, Eleonora Seelig¹, Katharina Timper¹, Mareike Cordes², Michael Coslovsky³, Henner Hanssen², Arno Schmidt-Trucksäss², Marc Y Donath¹

Affiliations

¹ Clinic of Endocrinology, Diabetes and Metabolism University Hospital Basel, and Department Biomedicine. University of Basel, 4031 Basel, Switzerland.
² Division of Sports and Exercise Medicine, Department of Sport, Exercise and Health, Medical Faculty, University of Basel, Basel, Switzerland.
³ Clinical Trial Unit, University Hospital Basel, 4031 Basel, Switzerland.

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.

Trial registration: ClinicalTrials.gov NCT01771445.

Publication types

Clinical Trial
Randomized Controlled Trial
Research Support, Non-U.S. Gov't

MeSH terms

Adult
C-Reactive Protein / analysis
Cell Line
Chemokines / metabolism
Cross-Over Studies
Diabetes Mellitus, Type 2 / blood
Diabetes Mellitus, Type 2 / metabolism
Diabetes Mellitus, Type 2 / pathology
Double-Blind Method
Exercise*
Humans
Insulin-Secreting Cells / cytology
Insulin-Secreting Cells / drug effects
Insulin-Secreting Cells / metabolism
Interleukin-1beta / genetics
Interleukin-1beta / metabolism
Interleukin-1beta / pharmacology
Interleukin-6 / blood*
Interleukin-8 / blood
Male
Middle Aged
Muscle, Skeletal / metabolism*
Placebo Effect
Receptors, Interleukin-1 / antagonists & inhibitors*
Receptors, Interleukin-1 / metabolism
Recombinant Proteins / biosynthesis
Recombinant Proteins / isolation & purification
Recombinant Proteins / pharmacology
Serum / chemistry

Substances

Chemokines
Interleukin-1beta
Interleukin-6
Interleukin-8
Receptors, Interleukin-1
Recombinant Proteins
C-Reactive Protein

Associated data

ClinicalTrials.gov/NCT01771445

Grants and funding

The study was supported by the Swiss National Foundation (www.snf.ch, MYD).