Strenuous exercise induces increased levels in a number of pro-and anti-inflammatory cytokines, natural occurring cytokine inhibitors, and chemokines. Thus, increased plasma levels of tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 beta, IL-1 receptor antagonist (IL-1ra), TNF-receptors (TNF-R), IL-10, IL-8, and macrophage inflammatory protein (MIP)-1 are found after strenuous exercise. The concentration of IL-6 increases as much as 100-fold after a marathon race. It has recently been demonstrated that IL-6 is produced locally in contracting skeletal muscles and that the net release from the muscle can account for the exercise-induced increase in arterial concentration. Larger amounts of IL-6 are produced in response to exercise than any other cytokine, IL-6 is produced locally in the skeletal muscle in response to exercise, and IL-6 is known to induce hepatic glucose output and to induce lipolysis. These facts indicate that IL-6 may represent an important link between contracting skeletal muscles and exercise-related metabolic changes.