Purpose of review: The concept of IL-6 as a deleterious interleukin was challenged by its anti-inflammatory actions.
Recent findings: The beneficial health effects of exercise and the crosstalk between insulin-sensitive tissues and insulin-producing cells are mediated by IL-6.
Summary: IL-6 displays pleiotropic functions in a tissue-specific and physiological context-dependent manner. There is evidence suggesting that IL-6 worsens insulin resistance in the liver and adipose tissue, while improving insulin sensitivity in the muscle. The effects of this cytokine are influenced by its acute or chronical presence, the latter being associated with insulin resistance. IL-6 has anti-inflammatory effects and a compensatory role in obesity by increasing islet GLP-1 production. The therapeutic approach of blocking IL-6 signal can be diabetogenic.