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Interleukin 6: from bench to bedside

Nature Clinical Practice Rheumatology volume 2, pages 619–626 (2006)Cite this article

An Erratum to this article was published on 01 December 2006

Abstract

Interleukin (IL)-6 is a pleiotropic cytokine that has important roles in the regulation of the immune response, inflammation, and hematopoiesis. Disruption of IL-6 regulation might, however, affect the immune response and consequently induce immune-mediated inflammatory diseases such as rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease, and Crohn's disease. Overproduction of IL-6 also contributes, through its roles as a growth factor or an antiapoptotic factor, to the development of malignant diseases such as multiple myeloma and renal cancer. Progress in the study of IL-6 has increased our understanding of the pathological roles of this cytokine in these diseases and provided key evidence that antagonizing its activities can be used as a therapeutic strategy. The application of molecular biology techniques to design monoclonal antibodies as therapeutic agents has made it possible to regulate the IL-6 signal to successfully treat diseases that have so far proved refractory to conventional therapies. Blocking IL-6 actions by use of a humanized antibody, tocilizumab, which targets the IL-6 receptor, has been proven to be therapeutically effective for rheumatoid arthritis, systemic juvenile idiopathic arthritis, Castleman disease and Crohn's disease. In this review, we discuss a paradigm of IL-6 from basic science to clinical use.

Key Points

  • IL-6 is a pleiotropic cytokine, which has important roles in the regulation of the immune response, inflammation, and hematopoiesis

  • Constitutive overproduction of IL-6, however, might cause immune-mediated inflammatory diseases, such as rheumatoid arthritis and systemic juvenile idiopathic arthritis

  • Successful treatment of these diseases with a humanized anti-IL-6 receptor antibody tocilizumab has proven the clinical benefit of IL-6 blockade, and has also confirmed the pathological roles of IL-6 in these diseases

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Figure 1: An overview of the IL-6 signaling pathway and its regulation.
Figure 2: Candidate diseases for the potential applications of anti-interleukin-6-receptor therapy are shown.

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Authors and Affiliations

  1. professors in the Laboratory of Immune Regulation in the Graduate School of Frontier Biosciences, Osaka University, Suita City, Japan

    Norihiro Nishimoto & Tadamitsu Kishimoto

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  1. Norihiro Nishimoto
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  2. Tadamitsu Kishimoto
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Corresponding author

Correspondence to Norihiro Nishimoto.

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Competing interests

N Nishimoto has received consulting fees from Chugai Pharmaceutic Co. Ltd. T Kishimoto holds a patent for tocilizumab, PCT publication no. WO92/19759 (reconstituted human antibody against human interleukin-6 receptor; corresponding patent family: European patent 0628639B; US patent 5795965; Japanese patent 3370324B).

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Nishimoto, N., Kishimoto, T. Interleukin 6: from bench to bedside. Nat Rev Rheumatol 2, 619–626 (2006). https://doi.org/10.1038/ncprheum0338

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