TY - JOUR
T1 - Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection
AU - Creeden, Justin Fortune
AU - Imami, Ali Sajid
AU - Eby, Hunter M
AU - Gillman, Cassidy
AU - Becker, Kathryn N
AU - Reigle, Jim
AU - Andari, Elissar
AU - Pan, Zhixing K
AU - O'Donovan, Sinead M
AU - McCullumsmith, Robert E
AU - McCullumsmith, Cheryl B
N1 - Copyright © 2021 The Authors. Published by Elsevier Masson SAS.. All rights reserved.
PY - 2021/6
Y1 - 2021/6
N2 - Hyperinflammatory response caused by infections such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases organ failure, intensive care unit admission, and mortality. Cytokine storm in patients with Coronavirus Disease 2019 (COVID-19) drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor complex nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and its downstream target gene interleukin 6 (IL6) which interacts with IL6 receptor (IL6R) and the IL6 signal transduction protein (IL6ST or gp130) to regulate intracellular inflammatory pathways. In this study, we compare transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knockdown) cell lines in order to identify a mechanism by which antidepressants such as fluoxetine demonstrate non-serotonergic, anti-inflammatory effects. Our results demonstrate a critical role for IL6ST and NF-kappaB Subunit 1 (NFKB1) in fluoxetine's ability to act as a potential therapy for hyperinflammatory states such as asthma, sepsis, and COVID-19.
AB - Hyperinflammatory response caused by infections such as Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) increases organ failure, intensive care unit admission, and mortality. Cytokine storm in patients with Coronavirus Disease 2019 (COVID-19) drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor complex nuclear factor kappa-light-chain-enhancer of activated B cells (NF-kappaB) and its downstream target gene interleukin 6 (IL6) which interacts with IL6 receptor (IL6R) and the IL6 signal transduction protein (IL6ST or gp130) to regulate intracellular inflammatory pathways. In this study, we compare transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knockdown) cell lines in order to identify a mechanism by which antidepressants such as fluoxetine demonstrate non-serotonergic, anti-inflammatory effects. Our results demonstrate a critical role for IL6ST and NF-kappaB Subunit 1 (NFKB1) in fluoxetine's ability to act as a potential therapy for hyperinflammatory states such as asthma, sepsis, and COVID-19.
KW - Anti-Inflammatory Agents/pharmacology
KW - Cytokine Receptor gp130/genetics
KW - Cytokine Release Syndrome/drug therapy
KW - Fluoxetine/pharmacology
KW - Humans
KW - NF-kappa B p50 Subunit/genetics
KW - SARS-CoV-2
KW - COVID-19 Drug Treatment
U2 - 10.1016/j.biopha.2021.111437
DO - 10.1016/j.biopha.2021.111437
M3 - Article
C2 - 33691249
SN - 0753-3322
VL - 138
SP - 111437
JO - Biomedicine and Pharmacotherapy
JF - Biomedicine and Pharmacotherapy
M1 - 111437
ER -
