Current Rheumatology Reviews

Dr. Serena Guiducci  
Department of Biomedicine, Division of Rheumatology
University of Florence
Florence
Italy

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IL-6 Signaling and its Blockade with a Humanized Anti-Interleukin-6 Receptor Antibody in Rheumatoid Arthritis: Advent of a New and Innovative Therapeutic Drug, Tocilizumab

Author(s): Yoshiyuki Ohsugi, Tadamitsu Kishimoto.

Abstract:

Interleukin (IL)-6 has many biological functions. It induces acute-phase reactants (CRP, SAA) and suppresses albumin. It induces hepcidin, which regulates iron recycling and absorption, causing iron-deficiency anemia. It induces synovial cells to express receptor activator of nuclear factor-κB ligand (RANKL) and secrete vascular endothelial growth factor (VEGF), leading to osteoclast differentiation and neovascularization. In mice, it promotes development of Th17 cells (a new type of T cell) and inhibits Treg cells. Imbalance between these T cells may contribute to RA pathogenesis. In various clinical studies in RA, IL-6 signaling pathway blockade by a recombinant humanized anti-IL-6 receptor antibody, tocilizumab (TCZ), dramatically improved clinical symptoms. TCZ prevented radiographic progression of joint destruction by inhibiting synovial hyperplasia and cartilage/bone resorption. TCZ improved hematological abnormalities, including hypergammaglobulinemia, autoantibodies, and elevation of erythrocyte sedimentation rate and acute phase proteins. TCZ also improved systemic symptoms such as fatigue, anemia, anorexia and fever, improving quality of life. Many patients achieved clinical remission associated with decreased serum IL-6. These findings suggest that the proinflammatory cytokine, IL-6, also affects basic autoimmunity and they confirm that IL-6 hyper-production is responsible for joint destruction and the above clinical symptoms. Here, we discuss IL-6 signaling and its blockade by TCZ in RA.

Keywords: Interleukin-6 receptor, tocilizumab, rheumatoid arthritis, clinical remission, anemia of inflammation, humanized antibody

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Article Details

VOLUME: 7
ISSUE: 4
Year: 2011
Page: [288 - 300]
Pages: 13
DOI: 10.2174/157339711798221068
Price: $58