Targeting Interleukin-6 Signaling in Clinic

Sujin Kang; Toshio Tanaka; Masashi Narazaki; Tadamitsu Kishimoto

doi:10.1016/j.immuni.2019.03.026

Targeting Interleukin-6 Signaling in Clinic

Immunity. 2019 Apr 16;50(4):1007-1023. doi: 10.1016/j.immuni.2019.03.026.

Authors

Sujin Kang¹, Toshio Tanaka², Masashi Narazaki³, Tadamitsu Kishimoto⁴

Affiliations

¹ Department of Immune Regulation, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, Japan.
² Medical Affairs Bureau, Osaka Habikino Medical Center, 3-7-1 Habikino, Habikino City, Osaka, Japan.
³ Department of Respiratory Medicine and Clinical Immunology, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita City, Osaka, Japan; Department of Immunopathology, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, Japan.
⁴ Department of Immune Regulation, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita City, Osaka, Japan. Electronic address: kishimoto@ifrec.osaka-u.ac.jp.

PMID: 30995492
DOI: 10.1016/j.immuni.2019.03.026

Abstract

Interleukin-6 (IL-6) is a pleiotropic cytokine with roles in immunity, tissue regeneration, and metabolism. Rapid production of IL-6 contributes to host defense during infection and tissue injury, but excessive synthesis of IL-6 and dysregulation of IL-6 receptor signaling is involved in disease pathology. Therapeutic agents targeting the IL-6 axis are effective in rheumatoid arthritis, and applications are being extended to other settings of acute and chronic inflammation. Recent studies reveal that selective blockade of different modes of IL-6 receptor signaling has different outcomes on disease pathology, suggesting novel strategies for therapeutic intervention. However, some inflammatory diseases do not seem to respond to IL-6 blockade. Here, we review the current state of IL-6-targeting approaches in the clinic and discuss how to apply the growing understanding of the immunobiology of IL-6 to clinical decisions.

Keywords: IL-6; IL-6 receptor; acute; cancer; chronic; gp130; inflammation.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Animals
Antibodies, Monoclonal / immunology
Antibodies, Monoclonal / therapeutic use*
Arthritis, Rheumatoid / drug therapy
Arthritis, Rheumatoid / immunology
Clinical Trials as Topic
Cytokine Receptor gp130 / antagonists & inhibitors
Cytokine Receptor gp130 / immunology
Humans
Inflammation / drug therapy*
Inflammation / immunology
Interleukin-6 / antagonists & inhibitors*
Interleukin-6 / biosynthesis
Interleukin-6 / deficiency
Interleukin-6 / immunology
Janus Kinases / antagonists & inhibitors
Janus Kinases / physiology
MAP Kinase Signaling System / drug effects
Mice
Mice, Knockout
Molecular Targeted Therapy*
Receptors, Interleukin-6 / immunology
Ribonucleases / deficiency
STAT3 Transcription Factor / physiology
Signal Transduction / drug effects*
Suppressor of Cytokine Signaling 1 Protein / physiology
Suppressor of Cytokine Signaling 3 Protein / physiology

Substances

Antibodies, Monoclonal
IL6 protein, human
Interleukin-6
Receptors, Interleukin-6
SOCS1 protein, human
SOCS3 protein, human
STAT3 Transcription Factor
STAT3 protein, human
Suppressor of Cytokine Signaling 1 Protein
Suppressor of Cytokine Signaling 3 Protein
interleukin-6, mouse
Cytokine Receptor gp130
Janus Kinases
Ribonucleases
Zc3h12a protein, mouse