IL-6 trans-signaling induces plasminogen activator inhibitor-1 from vascular endothelial cells in cytokine release syndrome

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 117; no. 36; pp. 22351 - 22356
• Main Authors: Kang, Sujin, Tanaka, Toshio, Inoue, Hitomi, Ono, Chikako, Hashimoto, Shoji, Kioi, Yoshiyuki, Matsumoto, Hisatake, Matsuura, Hiroshi, Matsubara, Tsunehiro, Shimizu, Kentaro, Ogura, Hiroshi, Matsuura, Yoshiharu, Kishimoto, Tadamitsu
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 08.09.2020
• Subjects: Adult; Aged; Antibodies, Monoclonal, Humanized - therapeutic use; Antigens; Bacteria; Bacterial diseases; Bacterial infections; Betacoronavirus; Biological Sciences; Burns - metabolism; Burns - pathology; Cell activation; Cell therapy; Cells, Cultured; Chimeric antigen receptors; Circuits; Coagulation; Coronavirus Infections - drug therapy; Coronavirus Infections - metabolism; Coronavirus Infections - pathology; Coronaviruses; COVID-19; Cytokine Release Syndrome - drug therapy; Cytokine Release Syndrome - metabolism; Cytokine Release Syndrome - pathology; Cytokines; Cytokines - blood; Cytokines - metabolism; Endothelial cells; Endothelial Cells - drug effects; Endothelial Cells - metabolism; Female; Humans; Immunotherapy; Inflammation; Inhibitors; Interleukin 10; Interleukin 6; Interleukin 8; Interleukin-6 - blood; Interleukin-6 - metabolism; Lymphocytes; Lymphocytes T; Male; Middle Aged; Molecular modelling; Monoclonal antibodies; Monocyte chemoattractant protein 1; Monocytes; Pandemics; Pathogenesis; Patients; Plasminogen Activator Inhibitor 1 - blood; Plasminogen Activator Inhibitor 1 - metabolism; Plasminogen activator inhibitors; Pneumonia, Viral - drug therapy; Pneumonia, Viral - metabolism; Pneumonia, Viral - pathology; Receptors, Interleukin-6 - antagonists & inhibitors; Receptors, Interleukin-6 - metabolism; Respiratory distress syndrome; Respiratory Distress Syndrome - metabolism; Respiratory Distress Syndrome - pathology; SARS-CoV-2; Sepsis; Sepsis - metabolism; Sepsis - pathology; Signal Transduction; Signaling; Viral diseases; COVID-19; tocilizumab; cytokine release syndrome; endothelial cell; IL-6

Cytokine release syndrome (CRS) is a life-threatening complication induced by systemic inflammatory responses to infections, including bacteria and chimeric antigen receptor T cell therapy. There are currently no immunotherapies with proven clinical efficacy and understanding of the molecular mechan...