The dichotomic role of single cytokines: Fine-tuning immune responses

[Display omitted] •Proinflammatory cytokines induce different mechanisms, such as autophagy and heme-oxygenase 1, associated with cell survival and anti-inflammatory effects.•The dichotomy of proinflammatory and anti-inflammatory cytokines depends on the context.•Cell metabolism and soluble factors from the microenvironment influence the the functions of cytokines.•The dichotomic effects of cytokines can be manipulated for the improvement of cytokine-based therapies. Cytokines are known for their pleiotropic effects. They can be classified by their function as pro-inflammatory, such as tumor necrosis factor (TNF), interleukin (IL) 1 and IL-12, or anti-inflammatory, like IL-10, IL-35 and transforming growth factor β (TGF-β). Though this type of classification is an important simplification for the understanding of the general cytokine’s role, it can be misleading. Here, we discuss recent studies that show a dichotomic role of the so-called pro and anti-inflammatory cytokines, highlighting that their function can be dependent on the microenvironment and their concentrations. Furthermore, we discuss how the back-and-forth interplay between cytokines and immunometabolism can influence the dichotomic role of inflammatory responses as an important target to complement cytokine-based therapies.