Source and kinetics of interleukin-6 in humans during exercise demonstrated by a minimally invasive model

The objective of this study was to use a novel and non-invasive model to explore whether: (1) exercise-induced increases in systemic levels of interleukin-6 (IL-6) and other cytokines can be ascribed to local production in working muscle; and (2) how acute release of retained blood from an exercised limb impacts on metabolites in the systemic circulation. On two experimental days, at least 3 weeks apart, six healthy moderately trained male subjects performed one-legged knee-extensor exercise for 2 h at 60% of their maximal workload. On one occasion venous outflow from the exercised leg was inhibited for 18 min by inflating a cuff around the thigh as proximally as possible immediately following exercise. On the control occasion venous outflow was not inhibited. Venous blood samples were collected from an arm vein at 2-min intervals after exercise. During inhibition of venous outflow from the exercised leg systemic plasma levels of IL-6 decreased within minutes to near pre-exercise levels, whereas plasma glucose levels increased to higher levels than without the cuff. After release of the cuff, systemic levels of IL-6 increased rapidly to match levels on the control occasion. On release of the cuff, plasma levels of free fatty acids (FFAs) declined more than without the cuff. In conclusion, the observed increase in systemic IL-6 plasma concentrations during exercise can be attributed to release from the working limb. Other potential sources of IL-6 outside the working limb do not contribute significantly to the increase in plasma IL-6 levels during exercise.