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This article is part of the supplement: The Scientific Basis of Rheumatology

Review

The paradigm of IL-6: from basic science to medicine

Tetsuji Naka1*, Norihiro Nishimoto2 and Tadamitsu Kishimoto3

Author Affiliations

1 Department of Molecular Medicine, Osaka University Graduate School of Medicine, Osaka, Japan

2 Department of Medical Science I, School of Health and Sport Sciences, Osaka University, Japan

3 Osaka University, Japan

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Arthritis Res 2002, 4(Suppl 3):S233-S242  doi:10.1186/ar565


London, UK. 24-26 June 2002

Published: 9 May 2002

Abstract

IL-6 is a pleiotropic cytokine with a wide range of biological activities in immune regulation, hematopoiesis, inflammation, and oncogenesis. Its activities are shared by IL-6-related cytokines such as leukemia inhibitory factor and oncostatin M. The pleiotropy and redundancy of IL-6 functions have been identified by using a unique receptor system comprising two functional proteins: an IL-6 receptor (IL-6R) and gp130, the common signal transducer of cytokines related to IL-6. Signal transduction through gp130 is mediated by two pathways: the JAK–STAT (Janus family tyrosine kinase–signal transducer and activator of transcription) pathway and the Ras mitogen-activated protein kinase pathway. The negative regulators of IL-6 signaling have also been identified, although the physiological roles of the molecules are not yet fully understood. The pathological roles of IL-6 have also been clarified in various disease conditions, such as inflammatory, autoimmune, and malignant diseases. On the basis of the findings, a new therapeutic approach to block the IL-6 signal using humanized anti-IL-6R antibody for rheumatoid arthritis, Castleman's disease, and multiple myeloma has been attempted.

Keywords:
cytokines; gp130; interleukin-6; SOCS; rheumatoid arthritis