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Fluoxetine as an Anti-Inflammatory Therapy in SARS-CoV-2 Infection

13 Pages Posted: 14 Dec 2020

See all articles by Justin Creeden

Justin Creeden

University of Toledo - Department of Neurosciences

Ali Sajid Imami

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo

Hunter M. Eby

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo

Cassidy Gillman

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences

Kathryn N. Becker

Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo

Jim Reigle

Department of Biomedical Informatics, University of Cincinnati College of Medicine

Elissar Andari

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences

Zhixing K. Pan

Department of Medical Microbiology and Immunology, University of Toledo Medical Center

Sinead M. O’Donovan

University of Toledo - Cognitive Disorders Research Laboratory

Robert E. McCullumsmith

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo

Cheryl B. McCullumsmith

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences

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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

Creeden, Justin and Imami, Ali Sajid and Eby, Hunter M. and Gillman, Cassidy and Becker, Kathryn N. and Reigle, Jim and Andari, Elissar and Pan, Zhixing K. and O’Donovan, Sinead M. and McCullumsmith, Robert E. and McCullumsmith, Cheryl B., Fluoxetine as an Anti-Inflammatory Therapy in SARS-CoV-2 Infection. Available at SSRN: https://ssrn.com/abstract=3736012 or http://dx.doi.org/10.2139/ssrn.3736012

Justin Creeden (Contact Author)

University of Toledo - Department of Neurosciences ( email )

Toledo, OH
United States

Ali Sajid Imami

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo ( email )

Hunter M. Eby

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo ( email )

Cassidy Gillman

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences ( email )

Kathryn N. Becker

Department of Cancer Biology, College of Medicine and Life Sciences, University of Toledo ( email )

Jim Reigle

Department of Biomedical Informatics, University of Cincinnati College of Medicine ( email )

Elissar Andari

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences ( email )

Zhixing K. Pan

Department of Medical Microbiology and Immunology, University of Toledo Medical Center ( email )

Sinead M. O’Donovan

University of Toledo - Cognitive Disorders Research Laboratory ( email )

Robert E. McCullumsmith

Department of Neurosciences, College of Medicine and Life Sciences, University of Toledo ( email )

Cheryl B. McCullumsmith

Department of Psychiatry, University of Toledo College of Medicine and Life Sciences ( email )