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Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms.
Exp Mol Med. 2021 07; 53(7):1116-1123.EM

Abstract

Interleukin-6 (IL-6) plays a crucial role in host defense against infection and tissue injuries and is a bioindicator of multiple distinct types of cytokine storms. In this review, we present the current understanding of the diverse roles of IL-6, its receptors, and its signaling during acute severe systemic inflammation. IL-6 directly affects vascular endothelial cells, which produce several types of cytokines and chemokines and activate the coagulation cascade. Endothelial cell dysregulation, characterized by abnormal coagulation and vascular leakage, is a common complication in cytokine storms. Emerging evidence indicates that a humanized anti-IL-6 receptor antibody, tocilizumab, can effectively block IL-6 signaling and has beneficial effects in rheumatoid arthritis, juvenile systemic idiopathic arthritis, and Castleman's disease. Recent work has also demonstrated the beneficial effect of tocilizumab in chimeric antigen receptor T-cell therapy-induced cytokine storms as well as coronavirus disease 2019 (COVID-19). Here, we highlight the distinct contributions of IL-6 signaling to the pathogenesis of several types of cytokine storms and discuss potential therapeutic strategies for the management of cytokine storms, including those associated with sepsis and COVID-19.

Authors+Show Affiliations

Laborabory of Immune Regulation, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan. kang@ifrec.osaka-u.ac.jp.Laborabory of Immune Regulation, Immunology Frontier Research Center, Osaka University, 3-1 Yamadaoka, Suita, Osaka, Japan. kishimoto@ifrec.osaka-u.ac.jp.

Pub Type(s)

Journal Article
Review

Language

eng

PubMed ID

34253862

Citation

Kang, Sujin, and Tadamitsu Kishimoto. "Interplay Between Interleukin-6 Signaling and the Vascular Endothelium in Cytokine Storms." Experimental & Molecular Medicine, vol. 53, no. 7, 2021, pp. 1116-1123.
Kang S, Kishimoto T. Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Exp Mol Med. 2021;53(7):1116-1123.
Kang, S., & Kishimoto, T. (2021). Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. Experimental & Molecular Medicine, 53(7), 1116-1123. https://doi.org/10.1038/s12276-021-00649-0
Kang S, Kishimoto T. Interplay Between Interleukin-6 Signaling and the Vascular Endothelium in Cytokine Storms. Exp Mol Med. 2021;53(7):1116-1123. PubMed PMID: 34253862.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Interplay between interleukin-6 signaling and the vascular endothelium in cytokine storms. AU - Kang,Sujin, AU - Kishimoto,Tadamitsu, Y1 - 2021/07/12/ PY - 2021/02/27/received PY - 2021/05/28/accepted PY - 2021/05/27/revised PY - 2021/7/14/pubmed PY - 2021/8/11/medline PY - 2021/7/13/entrez SP - 1116 EP - 1123 JF - Experimental & molecular medicine JO - Exp Mol Med VL - 53 IS - 7 N2 - Interleukin-6 (IL-6) plays a crucial role in host defense against infection and tissue injuries and is a bioindicator of multiple distinct types of cytokine storms. In this review, we present the current understanding of the diverse roles of IL-6, its receptors, and its signaling during acute severe systemic inflammation. IL-6 directly affects vascular endothelial cells, which produce several types of cytokines and chemokines and activate the coagulation cascade. Endothelial cell dysregulation, characterized by abnormal coagulation and vascular leakage, is a common complication in cytokine storms. Emerging evidence indicates that a humanized anti-IL-6 receptor antibody, tocilizumab, can effectively block IL-6 signaling and has beneficial effects in rheumatoid arthritis, juvenile systemic idiopathic arthritis, and Castleman's disease. Recent work has also demonstrated the beneficial effect of tocilizumab in chimeric antigen receptor T-cell therapy-induced cytokine storms as well as coronavirus disease 2019 (COVID-19). Here, we highlight the distinct contributions of IL-6 signaling to the pathogenesis of several types of cytokine storms and discuss potential therapeutic strategies for the management of cytokine storms, including those associated with sepsis and COVID-19. SN - 2092-6413 UR - https://www.unboundmedicine.com/medline/citation/34253862/Interplay_between_interleukin-6_signaling_and_the_vascular_endothelium_in_cytokine_storms. L2 - https://doi.org/10.1038/s12276-021-00649-0 DB - PRIME DP - Unbound Medicine ER -