IL-6 and its biological function

The multifunctional cytokine interleukin 6 (IL-6) was cloned in 1986. Since then, our understanding of its role in the regulatory functions in the immune system has grown steadily. IL-6 is a typical pleiotropic cytokine that acts on various cells. It is commonly produced at local tissue sites and is released in almost all situations of homeostatic perturbation, which include endotoxaemia, trauma, and acute infection. In addition, circulating IL-6, together with tumour necrosis factor α (TNF-α) and interleukin 1 (IL-1), is required for induction of the acute phase response which comprises fever, corticosteroid release, and hepatic production of acute phase proteins which are mostly protease inhibitors. Overall, induction of the acute phase response by IL-6 has been regarded as part of an attempt to maintain homeostasis. Apart from its role in inflammation, IL-6 induces differentiation and development of B cells, T cells, myeloid cells, megakaryocytes, osteoclasts, neural cells, and hepatocytes. IL-6 acts as a growth factor for renal cell carcinoma and Kaposi's sarcoma, and promotes the growth of haematopoietic stem cells.

Apart from the cytokine itself, the IL-6 family comprises IL-11, ciliary neurotrophic factor (CNTF), cardiotropin (CT-1), oncostatin M (OSM), leukaemia inhibitory factor (LIF), and the novel neurotrophin 1/B cell stimulating factor 3 (NNT-1/BSF-3), which all share the common signal transducer gp130 as part of their receptors. Except for CNTFR, the IL-6-type cytokine signalling receptors are type I membrane proteins (extracellular N terminus, one transmembrane domain). This receptor family is defined by the presence of at least one cytokine binding molecule (CBM), a set of four conserved tyrosine residues, and a tryptophan-serine-X-tryptophan-serine (W-S-X-S-W) motif, located outside the transmembrane domain. Signal transduction after ligand binding is elicited by homodimerisation of gp130 in the case of IL-6 and IL-11, by heterodimerisation of gp130 and LIFR in the case of LIF, CNTF and CT-1, …