lnterleukin-6 and Its Receptor; From Cloning to Clinic

Functional pleiotropy and redundancy are characteristic features of cytokines. Interleukin-6 (IL-6) is a typical example: IL-6 induces cellular differentiation or expression of tissue-specific genes; it is involved in processes such as antibody production in B cells, acute-phase protein synthesis in hepatocytes, megakaryocyte maturation, cytotoxic T cell differentiation, and neural differentiation of PC12 (pheochromocytoma) cells. It promotes growth of myeloma/ plasmacytoma cells, T cells, keratinocytes and renal mesangial cells, and it inhibits growth of myeloid leukemic cell lines and certain carcinoma cell lines. The IL-6 receptor consists of two polypeptide chains, a ligand-binding chain (IL-6R) and a non-ligand-binding, signal-transducing chain (gp130). Interaction of IL-6 with IL-6R triggers the association of gp130 and IL-6R, and the signal can be transduced through gp130. Association of gp130 with IL-6R is involved in the formation of high-affinity binding sites. gp130 was shown to be utilized as a signal transducer not only for IL-6R but also for several other cytokine receptors including LIF (leukemia inhibitory factor), OM (oncostatin M) CNTF (ciliary neurotropic factor) and IL-11. The pleiotropy and redundancy of cytokines may be explained on the basis of this unique receptor system.