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Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling
Simon A. Jones, … , Jürgen Scheller, Stefan Rose-John
Simon A. Jones, … , Jürgen Scheller, Stefan Rose-John
Published September 1, 2011
Citation Information: J Clin Invest. 2011;121(9):3375-3383. https://doi.org/10.1172/JCI57158.
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Science in Medicine

Therapeutic strategies for the clinical blockade of IL-6/gp130 signaling

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Abstract

The successful treatment of certain autoimmune conditions with the humanized anti–IL-6 receptor (IL-6R) antibody tocilizumab has emphasized the clinical importance of cytokines that signal through the β-receptor subunit glycoprotein 130 (gp130). In this Review, we explore how gp130 signaling controls disease progression and examine why IL-6 has a special role among these cytokines as an inflammatory regulator. Attention will be given to the role of the soluble IL-6R, and we will provide a perspective into the clinical blockade of IL-6 activity in autoimmunity, inflammation, and cancer.

Authors

Simon A. Jones, Jürgen Scheller, Stefan Rose-John

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Figure 2

Modes of therapeutic IL-6 blockade.

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Modes of therapeutic IL-6 blockade.
IL-6–neutralizing antibodies (violet...
IL-6–neutralizing antibodies (violet; Table 1) block both classical and trans-signaling of IL-6 by interfering with binding of IL-6 to IL-6R. This might lead to high-level accumulation of IL-6 due to decreased clearance. IL-6R–neutralizing antibodies interfere with binding of IL-6R to IL-6 (green; Table 1) and also block both classical and trans-signaling of IL-6 but only lead to moderate elevation of IL-6 levels due to impaired internalization and subsequent degradation of IL-6. The sgp130Fc protein (red/brown; Table 1) specifically blocks IL-6 trans-signaling without affecting classical signaling via the membrane-bound IL-6R, since IL-6 alone has no measurable affinity to sgp130Fc.

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