Anti-inflammatory action and effects on carbohydrate and lipid metabolism: an understudied role of interleukin-6.

Abstract

Interleukin-6 (IL-6) is a cytokine with pleiotropic effects that plays a significant role in the transition from the innate immune response to adaptive response. IL-6 is of interest due to its proinflammatory action, however, it also exhibits anti-inflammatory effects, supporting metabolism and suppressing associated diseases, such as obesity, diabetes mellitus and metabolic syndrome. The IL-6 receptor (IL-6R) is a type I transmembrane glycoprotein in the plasma membrane of only some cell types, such as macrophages, neutrophils, hepatocytes, and T cells. The function of IL-6R requires another transmembrane glycoprotein of 130 kDa (gp130) which, in contrast to IL-6R, is expressed in many cell types. In addition, a soluble form of the IL-6 receptor (sIL-6R) also plays a role in the function of IL-6. These receptors, gp130 and sIL-6R, are involved in the trans pathway of IL-6 signalling, the activation of which is associated with high IL-6 concentrations, promoting proinflammatory processes that are well known. In contrast, the physiological effects of IL-6 associated with increased insulin secretion, fatty acid oxidation and decreased adipose tissue, which occur due to activation of the IL-6 anti-inflammatory signalling pathway, have been poorly explored. Some studies using IL-6 knockout models suggest that some of the anti-inflammatory effects of IL-6 may be stimulated by low concentrations of IL-6, and are essential to suppressing metabolic alterations. This review seeks to highlight the importance of the anti-inflammatory role of IL-6 in metabolic diseases.