IL-6: from its discovery to clinical applications.

In the late 1960s, the essential role of T cells in antibody production was reported. This led to our hypothesis that T-cell-derived soluble factors would have to be involved in the activation of B cells. The factor that induced B cells to produce immunoglobulins was initially named B-cell stimulatory factor-2. In 1986, we successfully cloned the complementary DNA encoding B-cell stimulatory factor-2, now known as IL-6. At the same time, IFN-beta2 and a 26-kDa protein found in fibroblasts were independently cloned and found to be identical to IL-6. Later, a hybridoma/plasmacytoma growth factor and a hepatocyte-stimulating factor were also proven to be the same molecule as IL-6. Now, we know that IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation and oncogenesis. Since the discovery of IL-6, we have further clarified its activities, the IL-6R system and the IL-6 signal transduction mechanism. On the basis of the findings, a new therapeutic approach to block the actions of IL-6 by use of a humanized anti-IL-6R antibody has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis and Castleman's disease. In this review, I discuss the history of IL-6 research as a paradigm of progress from basic science to clinical applications.