Versatile functions for IL-6 in metabolism and cancer

•IL-6 has varied roles and its effects are highly context- and tissue-dependent.•IL-6 is largely beneficial for tissue homeostasis, with roles in resolving inflammation.•IL-6 has detrimental effects during carcinogenesis and in chronic inflammation. Owing to its abundance in inflammatory settings, interleukin IL-6 is frequently viewed as a proinflammatory cytokine, with functions that parallel those of tumor necrosis factor (TNF) and IL-1β in the context of inflammation. However, accumulating evidence points to a broader role for IL-6 in a variety of (patho)physiological conditions, including functions related to the resolution of inflammation. We review recent findings on the complex biological functions governed by IL-6 signaling, focusing on its role in inflammation-associated cancer and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We propose that the anti-inflammatory functions of IL-6 may extend to multiple settings and cell types, and suggest that these dimensions should be incorporated in therapeutic approaches to these diseases. Finally, we outline important areas of inquiry towards understanding this pleiotropic cytokine. Owing to its abundance in inflammatory settings, interleukin IL-6 is frequently viewed as a proinflammatory cytokine, with functions that parallel those of tumor necrosis factor (TNF) and IL-1β in the context of inflammation. However, accumulating evidence points to a broader role for IL-6 in a variety of (patho)physiological conditions, including functions related to the resolution of inflammation. We review recent findings on the complex biological functions governed by IL-6 signaling, focusing on its role in inflammation-associated cancer and metabolic disorders such as obesity and type 2 diabetes mellitus (T2DM). We propose that the anti-inflammatory functions of IL-6 may extend to multiple settings and cell types, and suggest that these dimensions should be incorporated in therapeutic approaches to these diseases. Finally, we outline important areas of inquiry towards understanding this pleiotropic cytokine.