Interleukin-6 and interleukin-11: same same but different

The pleiotropic physiological functions of interleukin (IL-) 6 type cytokines range from embryonic development and tissue homoeostasis to neuronal development and T cell differentiation. In contrast, imbalance of the well-controlled cytokine signaling network leads to chronic inflammatory diseases and cancer. IL-6 and IL-11 both signal through a homodimer of the ubiquitously expressed beta-receptor glycoprotein 130 (gp130). Specificity is gained through an individual IL-6/IL-11 alpha-receptor, which does not directly participate in signal transduction, although the initial cytokine binding event to the alpha-receptor leads to the final complex formation with the beta-receptors. Both cytokines activate the same downstream signaling pathways, which are predominantly the mitogen-activated protein kinase (MAPK)-cascade and the Janus kinase/signal transducer and activator of transcription (Jak/STAT) pathway. However, recent studies have highlighted divergent roles of the two related cytokines. Here, we will discuss how the biochemical similarities are translated into unique and non-redundant functions of IL-6 and IL-11 in vivo and illustrate strategies for cytokinespecific therapeutic intervention.