CP: Interleukin 6 in acute exercise and training; what is the biological relevance. Exerc Immunil Rev 2006, 12:6-33. doi: 10.1186/cc8987 Cite this article as: Routsi et al., Electrical muscle stimulation prevents critical illness polyneuromyopathy: a rand

It is now recognized that contracting skeletal muscle may synthesize and release interleukin-6 (IL-6) into the interstitium as well as into the systemic circulation in response to a bout of exercise. Although several sources of IL-6 have been demon-strated, contracting muscles contributes to most of the IL-6 present in the circula-tion in response to exercise. The magnitude of the exercise-induced IL-6 response is dependent on intensity and especially duration of the exercise, while the mode of exercise has little effect. Several mechanisms may link muscle contractions to IL-6 synthesis: Changes in calcium homeostasis, impaired glucose availability, and increased formation of reactive oxygen species (ROS) are all capable of acti-vating transcription factors known to regulate IL-6 synthesis. Via its effects on liver, adipose tissue, hypothalamic-pituitary-adrenal (HPA) axis and leukocytes, IL-6 may modulate the immunological and metabolic response to exercise. How-ever, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Fur-thermore, exercise training may reduce basal IL-6 production as well as the mag-nitude of the acute exercise IL-6 response by counteracting several potential stim-uli of IL-6. Accordingly, a decreased plasma IL-6 concentration at rest as well as in response to exercise appears to characterize normal training adaptation