Cytokine-targeted
therapy has generated a paradigm shift in the treatment of several immune-mediated diseases.
Interleukin-6 (IL-6), which was initially identified as
B-cell stimulatory factor 2, is a prototypical
cytokine with wide-ranging
biological effects on immune cells such as B and T cells, on hepatocytes, hematopoietic cells, vascular endothelial cells and on many others.
IL-6 is thus crucially involved in the regulation of immune responses, hematopoiesis and
inflammation. When
infections and tissue
injuries occur,
IL-6 is promptly synthesized and performs a protective role in host defense against such stresses and
traumas. However, excessive production of
IL-6 during this emergent process induces potentially fatal complications, including
systemic inflammatory response syndrome (SIRS), and dysregulated, persistently high expression of
IL-6 causes the onset or development of various chronic immune-mediated disorders. For these reasons,
IL-6 blockade was expected to become a novel therapeutic strategy for various diseases characterized by
IL-6 overproduction. Indeed, worldwide clinical trials of
tocilizumab, a humanized anti-IL-6 receptor
monoclonal antibody, have successfully proved its outstanding efficacy against
rheumatoid arthritis, juvenile idiopathic
arthritis and
Castleman disease, leading to the approval of
tocilizumab for the treatment of these diseases. Moreover, various reports regarding
off-label use of
tocilizumab strongly suggest that it will be widely applicable for acute, severe complications such as SIRS and
cytokine-release syndrome and other refractory chronic immune-mediated diseases.