Appreciating the Balance between Classical Interleukin (IL)-6 Receptor Signaling and IL-6 Trans-Signaling: Implications for Arthritis Progression

The humanized anti-interleukin (IL)-6 receptor antibody Tocilizumab is currently in Phase III clinical trials for use in autoimmune conditions such as rheumatoid arthritis and Crohn's disease. However do we fully appreciate the regulation of IL-6 responses in vivo, and understand the wider implications of IL-6 bioactivity in general physiology and inflammation? In the context of this review we will explore how IL-6 affects arthritis progression, and discuss the inflammatory mechanism governing IL-6 responsiveness. Specific attention will be given to the role of the soluble IL-6 receptor and we will discuss the merit of selectively targeting this soluble receptor as an alternative therapeutic strategy for clinically blocking IL-6 involvement in disease.