A new era for the treatment of inflammatory autoimmune diseases by interleukin-6 blockade strategy

Semin Immunol. 2014 Feb;26(1):88-96. doi: 10.1016/j.smim.2014.01.009. Epub 2014 Mar 1.


Interleukin-6 (IL-6) is a cytokine with redundant and pleiotropic activities, and its synthesis is tightly regulated by transcriptional and posttranscriptional mechanisms. When infections and tissue injuries occur, IL-6 synthesis is promptly induced and provides an emergent signal that contributes to host defense through the stimulation of acute-phase responses, immune reactions, and hematopoiesis. After the environmental stress is removed from the host, the production of IL-6 is terminated. However, dysregulated continual synthesis of IL-6 is involved in the development of chronic inflammatory autoimmune diseases. For this reason, tocilizumab, a humanized anti-IL-6 receptor antibody, was developed. Worldwide clinical trials have demonstrated the outstanding efficacy of tocilizumab in rheumatoid arthritis, systemic juvenile idiopathic arthritis, and Castleman's disease; thus, a new era has come for the treatment of these diseases, which were previously considered intractable. Moreover, favorable results from off-label use of tocilizumab strongly suggest that it will be widely applicable for various refractory inflammatory autoimmune diseases. In this context, the mechanism for the continual synthesis of IL-6 needs to be elucidated in order to investigate the pathogenesis of specific diseases and to facilitate the development of more specific therapeutic strategies.

Keywords: Autoimmunity; IL-6; Inflammation; Tocilizumab.

Publication types

  • Review

MeSH terms

  • Acute-Phase Proteins / biosynthesis
  • Animals
  • Antibodies, Monoclonal / pharmacology
  • Antibodies, Monoclonal / therapeutic use*
  • Antibodies, Monoclonal, Humanized / pharmacology
  • Antibodies, Monoclonal, Humanized / therapeutic use
  • Autoimmune Diseases / drug therapy*
  • Autoimmune Diseases / genetics
  • Autoimmune Diseases / immunology
  • Autoimmune Diseases / metabolism*
  • Gene Expression Regulation / drug effects
  • Humans
  • Immunomodulation / drug effects
  • Inflammation / drug therapy*
  • Inflammation / genetics
  • Inflammation / immunology
  • Inflammation / metabolism*
  • Interleukin-6 / genetics
  • Interleukin-6 / metabolism*
  • RNA Processing, Post-Transcriptional
  • Receptors, Interleukin-6 / antagonists & inhibitors
  • Receptors, Interleukin-6 / metabolism
  • Signal Transduction / drug effects*
  • Transcription, Genetic


  • Acute-Phase Proteins
  • Antibodies, Monoclonal
  • Antibodies, Monoclonal, Humanized
  • Interleukin-6
  • Receptors, Interleukin-6
  • tocilizumab