Generation of Soluble Interleukin-11 and Interleukin-6 Receptors: A Crucial Function for Proteases during Inflammation

Abstract EN

The cytokines interleukin-11 (IL-11) and IL-6 are important proteins with well-defined pro- and anti-inflammatory functions.

They activate intracellular signaling cascades through a homodimer of the ubiquitously expressed signal-transducing β-receptor glycoprotein 130 (gp130).

Specificity is gained through the cell- and tissue-specific expression of the nonsignaling IL-11 and IL-6 α-receptors (IL-11R and IL-6R), which determine the responsiveness of the cell to these two cytokines.

IL-6 is a rare example, where its soluble receptor (sIL-6R) has agonistic properties, so that the IL-6/sIL-6R complex is able to activate cells that are usually not responsive to IL-6 alone (trans-signaling).

Recent evidence suggests that IL-11 can signal via a similar trans-signaling mechanism.

In this review, we highlight similarities and differences in the functions of IL-11 and IL-6.

We summarize current knowledge about the generation of the sIL-6R and sIL-11R by different proteases and discuss possible roles during inflammatory processes.

Finally, we focus on the selective and/or combined inhibition of IL-6 and IL-11 signaling and how this might translate into the clinics.