Muscle-Derived Il-6 Is Not Regulated By Il-1 During Exercise. A Double Blind, Placebo-Controlled, Randomized Crossover Study

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.