Importance of soluble cytokine receptors for inflammation associated cancer

Cytokine receptors, which exist in membrane-bound and soluble form, bind their ligands with comparable affinity. While most soluble receptors are antagonists in that they compete for the ligands with their membrane counterparts, some soluble receptors are agonists. In this case, the complex of ligand and soluble receptor binds on target cells to a second receptor subunit and initiates signal transduction. The soluble receptors of the IL-6 family of cytokines (sIL-6R, sIL-11R, sCNTF-R) are agonists. In vivo, the IL-6/soluble IL-6R complex stimulates several types of target cells not stimulated by IL-6 alone, since they do not express membrane-bound IL-6R. This process has been named transsignalling. We have shown that in several chronic inflammatory diseases such as chronic inflammatory bowl disease, peritonitis and rheumatoid arthritis, transsignalling via soluble IL-6R complexed to IL-6 is a crucial point in the transition from the acute to the chronic state of the disease. The mechanism by which the IL-6/ soluble IL-6R complex regulates the inflammatory state is discussed.