The hormetic and hermetic role of IL-6

Interleukin-6 is a pleiotropic cytokine regulating different tissues and organs in diverse and sometimes discrepant ways. The dual and sometime hermetic nature of IL-6 action has been highlighted in several contexts and can be explained by the concept of hormesis, in which beneficial or toxic effects can be induced by the same molecule depending on the intensity, persistence, and nature of the stimulation. According with hormesis, a low and/or controlled IL-6 release is associated with anti-inflammatory, antioxidant, and pro-myogenic actions, whereas increased systemic levels of IL-6 can induce pro-inflammatory, pro-oxidant and pro-fibrotic responses. However, many aspects regarding the multifaceted action of IL-6 and the complex nature of its signal transduction remains to be fully elucidated. In this review we collect mechanistic insight into the molecular networks contributing to normal or pathologic changes during advancing age and in chronic diseases. We point out the involvement of IL-6 deregulation in aging-related diseases, dissecting the hormetic action of this key mediator in different tissues, with a special focus on skeletal muscle. Since IL-6 can act as an enhancer of detrimental factor associated with both aging and pathologic conditions, such as chronic inflammation and oxidative stress, this cytokine could represent a “Gerokine”, a determinant of the switch from physiologic aging to age-related diseases. •The actions of IL-6 differ depending on level/persistence of signal transduction.•IL-6 signalling pathways are mediated by different receptor complexes.•IL-6 signalling may represent a key pathway involved in aging and diseases.