Tocilizumab: blockade of interleukin-6 signaling pathway as a therapeutic strategy for inflammatory disorders

Interleukin (IL)-6 contributes to a myriad of physiologic and pathophysiologic processes. Among its many physiologic functions, IL-6 plays an active role in immunology, inflammatory responses, bone metabolism, arthritis and neoplasia. Overproduction of IL-6 has been implicated in the disease pathology of several inflammatory and autoimmune disorders, including rheumatoid arthritis, Castleman's disease, Crohn's disease and systemic-onset juvenile idiopathic arthritis. Interception of the IL-6 signaling pathway could thus represent a new treatment option for these diseases, given their refractory status to conventional therapy. Clinical studies with tocilizumab, a humanized monoclonal anti-IL-6 receptor antibody, have been undertaken to explore this option. Current short-term results indicate that tocilizumab dramatically improves disease activity and is well tolerated. Further long-term safety and efficacy studies are needed to confirm the therapeutic benefit of this antibody in inflammatory and autoimmune disorders.