tetano
Editor, Senior Moderator
Biomed Pharmacother
. 2021 Feb 25;138:111437.
doi: 10.1016/j.biopha.2021.111437. Online ahead of print.
Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection
Justin Fortune Creeden[SUP] 1 [/SUP], Ali Sajid Imami[SUP] 2 [/SUP], Hunter M Eby[SUP] 2 [/SUP], Cassidy Gillman[SUP] 3 [/SUP], Kathryn N Becker[SUP] 4 [/SUP], Jim Reigle[SUP] 5 [/SUP], Elissar Andari[SUP] 3 [/SUP], Zhixing K Pan[SUP] 6 [/SUP], Sinead M O'Donovan[SUP] 2 [/SUP], Robert E McCullumsmith[SUP] 7 [/SUP], Cheryl B McCullumsmith[SUP] 3 [/SUP]
Affiliations
Abstract
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.
Keywords: Antidepressants; COVID-19; Coronavirus disease 2019; Cytokine IL6; Cytokine storm; Fluoxetine; Inflammation; Nuclear factor kappa B subunit 1; SARS-CoV-2; SSRIs; Selective serotonin reuptake inhibitors; Sepsis; Severe acute respiratory syndrome coronavirus 2; Transcription factor NF-?B.
. 2021 Feb 25;138:111437.
doi: 10.1016/j.biopha.2021.111437. Online ahead of print.
Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection
Justin Fortune Creeden[SUP] 1 [/SUP], Ali Sajid Imami[SUP] 2 [/SUP], Hunter M Eby[SUP] 2 [/SUP], Cassidy Gillman[SUP] 3 [/SUP], Kathryn N Becker[SUP] 4 [/SUP], Jim Reigle[SUP] 5 [/SUP], Elissar Andari[SUP] 3 [/SUP], Zhixing K Pan[SUP] 6 [/SUP], Sinead M O'Donovan[SUP] 2 [/SUP], Robert E McCullumsmith[SUP] 7 [/SUP], Cheryl B McCullumsmith[SUP] 3 [/SUP]
Affiliations
- PMID: 33691249
- DOI: 10.1016/j.biopha.2021.111437
Abstract
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.
Keywords: Antidepressants; COVID-19; Coronavirus disease 2019; Cytokine IL6; Cytokine storm; Fluoxetine; Inflammation; Nuclear factor kappa B subunit 1; SARS-CoV-2; SSRIs; Selective serotonin reuptake inhibitors; Sepsis; Severe acute respiratory syndrome coronavirus 2; Transcription factor NF-?B.