**6. Interleukin 6**

Interleukin 6 (IL-6) is known to be secreted by several tissues; it is a pleiotropic cytokine with complex roles in metabolic and cardiovascular disease. IL-6 also can act in a local fashion. However, adipose tissue is a major source of this protein, capable of producing high levels of this protein in the blood. It has been estimated that as much as one-third of total circulating IL-6 originates from adipose tissue. Therefore, IL-6 can be considered an adipokine with endocrine actions.

IL-6-induced cell signaling is typically classified as either classic or transsignaling, and it can lead to different cell responses. In the classic signaling way, the target cells are stimulated by IL-6 stimulates via a membrane-bound IL-6 receptor (IL6R), which upon ligand binding forms a complex with the signaling receptor protein gp130. Essentially all cells exhibit gp130 on the cell surface, whereas few cell types express membrane-bound IL6R. While the cells that only express gp130 are not responsive to IL-6 alone, they can be stimulated, via trans-signaling, by a complex of IL-6 bound to a naturally occurring soluble form of IL6R (sIL6R), markedly expanding the spectrum of IL-6 actions and target cells.
