Question

Summarise the timecourse of the IL-6 response to an acute bout of prolonged strenuous exercise, and evaluate the major source of IL-6 secreted in response to exercise and the purpose of its secretion. (200 words)

Answer 1

Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the IL6 gene

Function. IL-6 is an important mediator of fever and of the acute phase response. It is capable of crossing the blood-brain barrier and initiating synthesis of PGE2 in the hypothalamus, thereby changing the body's temperature setpoint.
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 demonstrated, contracting muscles contributes to most of the IL-6 present in the circulation 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 activating 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. However, prolonged exercise involving a significant muscle mass in the contractile activity is necessary in order to produce a marked systemic IL-6 response. Furthermore, exercise training may reduce basal IL-6 production as well as the magnitude of the acute exercise IL-6 response by counteracting several potential stimuli 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.

IL-6 is released into the circulation during exercise.
Exercise training reduces visceral adipose tissue mass and this effect of exercise is abolished in the presence of IL-6 blockade.
IL-6 delays the rate of gastric emptying and reduces postprandial glycemia and insulin secretion in humans.
IL-6 reduces appetite through actions in the CNS.
Voluntary running suppresses tumor growth through epinephrine-dependent and IL-6-dependent NK cell mobilization and redistribution