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Fluoxetine as an Anti-Inflammatory Therapy in SARS-CoV-2 Infection
13 Pages Posted: 14 Dec 2020
More...Abstract
Hyperinflammatory response as a result of infections such as Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) increase organ failure, intensive care unit admission, and mortality. Cytokine storm in Coronavirus disease (COVID19) patients drives this pattern of poor clinical outcomes and is dependent upon the activity of the transcription factor NF-kB and its downstream target gene which encodes cytokine IL6. In this study, we compare publicly available transcriptomic signatures from a variety of drug-treated or genetically suppressed (i.e. knock down or knock out) cell lines in order to identify a mechanism by which antidepressants like fluoxetine demonstrate non-serotonergic anti-inflammatory effects. Our results demonstrate a critical role for the IL-6 Signal Transduction (IL-6ST or gp130) protein in fluoxetine’s ability to act as a potential therapy for hyperinflammatory states such as asthma and sepsis.
Funding: This research was supported by NIMH R01 MH107487, NIH R01 AG057598, and NIMH R01 MH121102, as well as the University of Toledo Foundation
Conflict of Interest: None to declare
Keywords: Cytokine IL-6, transcription factor NF-κB, inflammation, cytokine storm, antidepressants, fluoxetine, selective serotonin reuptake inhibitors, SSRIs, severe acute respiratory syndrome coronavirus 2, SARS-CoV-2, coronavirus disease, COVID-19, sepsis
Suggested Citation: Suggested Citation