Molecular Biology of Cells

Abstract

Interleukin 6 (IL-6) was originally discovered as T cell–derived B cell stimulatory factor-2, which promotes immunoglobulin synthesis by activated B-cells. Successful cloning of the gene for IL-6, followed by clarification of the entire IL-6 signaling pathway, led to an understanding of the molecular mechanisms of the characteristic features of cytokines, redundancy and pleiotropic activity. Importantly, transient expression of IL-6 was found to contribute to host defense against infections and tissue injury, whereas dysregulated continual synthesis of IL-6 has a pathological effect on various autoimmune inflammatory diseases. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Worldwide clinical trials have shown the outstanding efficacy of tocilizumab, resulting in its approval for the treatment of rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman disease. Tocilizumab is expected to be widely applicable for other intractable autoimmune inflammatory diseases.