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-κB.
【저자키워드】 COVID-19, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, Inflammation, Coronavirus disease 2019, Cytokine storm, Sepsis, antidepressants, Cytokine IL6, Fluoxetine, Nuclear factor kappa B subunit 1, SSRIs, Selective serotonin reuptake inhibitors, Transcription factor NF-κB., 【초록키워드】 coronavirus disease, severe acute respiratory syndrome coronavirus 2, Asthma, Coronavirus disease 2019, Cytokine storm, coronavirus, Anti-inflammatory effects, Mortality, intensive care, Infection, IL6, Sepsis, drug, antidepressants, severe acute respiratory syndrome Coronavirus, coronavirus 2, interleukin 6, Clinical outcome, B cell, Protein, Patient, receptor, respiratory, disease, Admission, Critical, mechanism, Signal transduction, NF-κB, intensive care unit admission, Hyperinflammatory response, hyperinflammatory state, cell lines, regulate, Fluoxetine, inflammatory pathways, Organ failure, transcription factor, target gene, Serotonin, acute respiratory syndrome, subunit, acute respiratory syndrome coronavirus, complex, IL6R, IL6ST, knockdown, NFkB1, cell line, potential therapy, downstream, nuclear, transcriptomic, gp130, identify, caused, activated, increase, variety, interact, suppressed, 【제목키워드】 SARS-COV-2 infection, Fluoxetine, Anti-inflammatory therapy,