title: Tocilizumab, a humanized anti-interleukin-6 receptor antibody, for treatment of rheumatoid arthritis.
abstract: Interleukin (IL)-6 has a variety of biological functions. For example, it stimulates the production of acute-phase reactants (C-reactive protein and serum amyloid A) and hepcidin which interferes with iron recycling and absorption, causing iron-deficient anemia, and augments expression of vascular endothelial growth factor and receptor activator of nuclear factor-κB ligand in synovial cells, leading to neovascularization and osteoclast formation. IL-6 also acts on lymphocytes, not only on B cells to stimulate autoantibody production, but also on naïve T helper cells to promote Th17 cell differentiation. Thus, an imbalance between T cell subsets possibly contributes to development of rheumatoid arthritis. Several clinical studies have demonstrated that a humanized anti-IL-6 receptor antibody, tocilizumab, improves clinical symptoms in rheumatoid arthritis. Tocilizumab prevented radiographic progression of joint destruction by inhibiting cartilage/bone resorption. Tocilizumab also improved hematological abnormalities, including hypergammaglobulinemia, high levels of autoantibodies, and elevation of erythrocyte sedimentation rate and acute-phase proteins. Importantly, tocilizumab improved quality of life by reducing systemic symptoms, including fatigue, anemia, anorexia, and fever. These findings have confirmed that hyperproduction of IL-6 is responsible for the above clinical symptoms, including joint destruction. Many patients treated with tocilizumab achieved clinical remission associated with decreased serum IL-6, suggesting that IL-6 enhances autoimmunity. Tocilizumab is a new therapeutic option for rheumatoid arthritis.
authors: Product Research Department, Chugai Pharmaceutical Co Ltd, Fuji-Gotemba Research Laboratories, Shizuoka, Japan.
authors: Masahiko
authors: M
authors: Mihara
authors: Chugai Pharmaceutical Co Ltd, Tokyo, Japan.
authors: Yoshiyuki
authors: Y
authors: Ohsugi
authors: Laboratory of Immunoregulation, Graduate School of Frontier Biosciences, Osaka University, Osaka, Japan.
authors: Tadamitsu
authors: T
authors: Kishimoto
keywords: efficacy; interleukin-6; mode of action; safety; tocilizumab