{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"omics_type":["Unknown"],"volume":["13"],"submitter":["Hu T"],"pubmed_abstract":["Cytokine release syndrome (CRS) is one of the leading causes of morbidity and mortality in COVID-19 patients with elevated levels of circulating cytokines contributing to various clinical symptoms. Favorable control of CRS represents a promising and effective strategy to mitigate the clinical outcomes of hospitalized patients with moderate to severe pneumonia. Using <i>in vivo</i> cytokine release assay in human peripheral blood mononuclear cell (PBMC)-engrafted immunodeficient mice, we reported that 17α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestogen, exhibited significant inhibition of OKT-3-stimulated production of numerous cytokines including TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, and GM-CSF. Furthermore, 17-OHPC inhibited <i>in vitro</i> production of IFN-γ, IL-1β, IL-2, IL-6, and IL-10 in human PBMCs stimulated with OKT3, while exhibiting down-regulation of the mRNA levels of TNF-α, IFN-γ, IL-2, IL-6, and IL-10. Using the same human PBMCs, additional stimulators anti-CD28 antibody or PHA treatments led to substantial cytokine production, which was also attenuated by 17-OHPC. OKT3-stimulated phosphorylation of IκBα and nuclear translocation of NF-κB p65 in human PBMCs were also reversed by 17-OHPC, suggesting its inhibition on NF-κB signaling in immune cells. Taken together, this work reported both <i>in vivo</i> and <i>in vitro</i> inhibition of cytokine production by 17-OHPC, presumably by virtue of its suppression of NF-κB signaling. These findings provide pharmacological evidence to support the potential application of 17-OHPC in treating CRS associated with COVID-19."],"journal":["Frontiers in pharmacology"],"pagination":["831315"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC8940231"],"repository":["biostudies-literature"],"pubmed_title":["17α-Hydroxyprogesterone Caproate Inhibits Cytokine Production via Suppression of NF-κB Activation."],"pmcid":["PMC8940231"],"pubmed_authors":["Hu T","Yang L","Du T","Tang C","Stern S"],"additional_accession":[]},"is_claimable":false,"name":"17α-Hydroxyprogesterone Caproate Inhibits Cytokine Production via Suppression of NF-κB Activation.","description":"Cytokine release syndrome (CRS) is one of the leading causes of morbidity and mortality in COVID-19 patients with elevated levels of circulating cytokines contributing to various clinical symptoms. Favorable control of CRS represents a promising and effective strategy to mitigate the clinical outcomes of hospitalized patients with moderate to severe pneumonia. Using <i>in vivo</i> cytokine release assay in human peripheral blood mononuclear cell (PBMC)-engrafted immunodeficient mice, we reported that 17α-hydroxyprogesterone caproate (17-OHPC), a synthetic progestogen, exhibited significant inhibition of OKT-3-stimulated production of numerous cytokines including TNF-α, IFN-γ, IL-2, IL-4, IL-6, IL-10, and GM-CSF. Furthermore, 17-OHPC inhibited <i>in vitro</i> production of IFN-γ, IL-1β, IL-2, IL-6, and IL-10 in human PBMCs stimulated with OKT3, while exhibiting down-regulation of the mRNA levels of TNF-α, IFN-γ, IL-2, IL-6, and IL-10. Using the same human PBMCs, additional stimulators anti-CD28 antibody or PHA treatments led to substantial cytokine production, which was also attenuated by 17-OHPC. OKT3-stimulated phosphorylation of IκBα and nuclear translocation of NF-κB p65 in human PBMCs were also reversed by 17-OHPC, suggesting its inhibition on NF-κB signaling in immune cells. Taken together, this work reported both <i>in vivo</i> and <i>in vitro</i> inhibition of cytokine production by 17-OHPC, presumably by virtue of its suppression of NF-κB signaling. These findings provide pharmacological evidence to support the potential application of 17-OHPC in treating CRS associated with COVID-19.","dates":{"release":"2022-01-01T00:00:00Z","publication":"2022","modification":"2025-04-04T22:12:59.582Z","creation":"2025-04-04T22:12:59.582Z"},"accession":"S-EPMC8940231","cross_references":{"pubmed":["35330839"],"doi":["10.3389/fphar.2022.831315"]}}