Other Affected Tissues
 Other tissues besides fat and the liver are affected by IL-6 that relate to body fat and chronic diseases. Skeletal muscle is a site of IL-6 production, and the amount of IL-6 generated is greatly increased by exercise. Cell studies and biopsies from subjects infused with IL-6 demonstrate that exercise can increase skeletal muscle production of IL-6 by 100 times. Skeletal muscle IL-6 production is stimulated by the muscle contracting and the influx of calcium that rushes into the muscle cell. The degree of IL-6 production appears to be related to the intensity of the exercise, as rowers (intense group) experience a two-fold increase in blood IL-6 within six minutes of exercise, whereas long-distance runners don’t show an IL-6 peak until after exercise ends. Also, it’s been shown that IL-6 peaks higher when glycogen is low, possibly suggesting one pathway for the greater fat loss seen in low-carbohydrate diets.

 IL-6 not only activates lipolysis in exercising muscle, but also increases the rate of fat oxidation (burning fat for calories). Contrary to other tissues, IL-6 doesn’t interfere with the insulin signal, allowing exercised muscle to take in sugar and Amino Acids from the blood. Other tissues become insulin resistant when exposed to IL-6 (this will be discussed later). IL-6 may also act as an anti-inflammatory signal in exercised muscle. Another cytokine, called tumor necrosis factor alpha (TNF), causes insulin resistance in many tissues, including skeletal muscle. In the presence of exercise-elevated IL-6, TNF production is markedly suppressed in that tissue. This is important, because IL-6 and TNF production are both stimulated by epinephrine (adrenalin), which is present in high concentrations during exercise. Without the anti-inflammatory effect of IL-6, skeletal muscle would become insulin resistant following exercise, interfering with glycogen replenishment, amino acid uptake and repair.  The brain is another important site of IL-6 action. Though the experiment hasn’t been attempted on humans, it’s been shown in animals that infusing IL-6 into the fluid surrounding the brain reduces appetite and leads to weight loss. It’s likely that this is also a mechanism of action in humans, as obese individuals have lower levels of IL-6 in the fluid surrounding the brain and spinal cord.