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Abstract
IL-6 is a pleiotropic cytokine that regulates haematopoiesis, inflammation and the immune response. The IL-6 receptor consists of an α chain and gp130, a common subunit that is shared among the receptors of the IL-6 family of cytokines. The binding of IL-6 to its receptor induces the homodimerisation of gp130, resulting in the activation of JAKs (Janus kinases). A variety of signal transduction pathways, such as those mediated by SHP2 and STAT3 (signal transducer and activator of transcription), are then activated. Because both the overexpression of IL-6 and the aberrant activation of the gp130 signal have been implicated in the pathology of a variety of diseases, including rheumatoid arthritis (RA), juvenile chronic arthritis, multiple myeloma/plasmacytoma, Castleman’s disease and Kaposi’s sarcoma, the development of inhibitors of the IL-6 signalling pathway is a promising avenue for the treatment of these diseases. Several approaches have been taken to inhibit the activation of this pathway. One is to interfere with the formation of the IL-6/IL-6Rα/gp130 complex. This strategy has already been used to improve the symptoms of patients with RA, multiple myeloma and Castleman’s disease. Another is the direct targeting of STAT3 activity. Here, we describe the biological activity of IL-6 and of the signal transduction pathways mediated through the IL-6 receptor, and discuss the possible therapeutic applications of IL-6 inhibitors.