ArticleInternational immunopharmacology2015
Paroxetine differentially modulates LPS-induced TNFα and IL-6 production in mouse macrophages.
Article in International immunopharmacology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04570449 (Fluoxetine to Reduce Hospitalization From COVID-19 Infection), which is not on this map. Cited by 29 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Fluoxetine to Reduce Hospitalization From COVID-19 Infection (FloR COVID-19)
Who cites it
29 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Peripheral Alterations in Cytokine and Chemokine Levels After Antidepressant Drug Treatment for Major Depressive Disorder: Systematic Review and Meta-Analysis.Molecular neurobiology · 2018Pooled it
- Trial
- Repurposing Selective Serotonin Reuptake Inhibitors as Immunomodulators: Effects on Macrophage Activation and Polarization.Molecular neurobiology · 2026Review
- Article
- Paroxetine attenuated liver fibrosis in liver of bile duct ligated rats: role of P2XNaunyn-Schmiedeberg's archives of pharmacology · 2025Article
- Paroxetine suppresses 27-hydroxycholesterol-induced responses in THP-1 human monocytic cells by regulating the AKT/mTORC1 pathway.Scientific reports · 2025Article
- Fluoxetine promotes IL-10-dependent metabolic defenses to protect from sepsis-induced lethality.Science advances · 2025Article
- Potential cardioprotective effect of paroxetine against ventricular remodeling in an animal model of myocardial infarction: a comparative study.BMC pharmacology & toxicology · 2024Article
- Neoastilbin ameliorates sepsis-induced liver and kidney injury by blocking the TLR4/NF-κB pathway.Histology and histopathology · 2024Article
- Fluoxetine promotes immunometabolic defenses to mediate host-pathogen cooperation during sepsis.bioRxiv : the preprint server for biology · 2023Article
- Paroxetine's effect on the proinflammatory cytokine stimulation and intracellular signaling pathways in J774.2 cells.Naunyn-Schmiedeberg's archives of pharmacology · 2023Article
- Correlation of systemic immune-inflammation index and moderate/major depression in patients with depressive disorders: a large sample cross-sectional study.Frontiers in psychiatry · 2023Article
- DNA repair proteins as the targets for paroxetine to induce cytotoxicity in gastric cancer cell AGS.American journal of cancer research · 2022Article
- Selective serotonin reuptake inhibitors: New hope in the fight against COVID-19.Frontiers in pharmacology · 2022Review
- Profiling Differential Effects of 5 Selective Serotonin Reuptake Inhibitors on TLRs-Dependent and -Independent IL-6 Production in Immune Cells Identifies Fluoxetine as Preferred Anti-Inflammatory Drug Candidate.Frontiers in pharmacology · 2022Article
- SSRIs: Applications in inflammatory lung disease and implications for COVID-19.Neuropsychopharmacology reports · 2021Review
- Article
- Suppression of cigarette smoke induced MMP1 expression by selective serotonin re-uptake inhibitors.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2021Article
- Fluoxetine as an anti-inflammatory therapy in SARS-CoV-2 infection.Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie · 2021Article
- Fisetin alleviates sepsis-induced multiple organ dysfunction in mice via inhibiting p38 MAPK/MK2 signaling.Acta pharmacologica Sinica · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Paroxetine is a selective serotonin reuptake inhibitor (SSRI) that is clinically used for the treatment of depression in human patients. Because of recent reports on the role of serotonin in modulating inflammation and the link between inflammation and depression, we sought to test the effect of paroxetine directly on macrophage response to an inflammatory stimulus. Lipopolysaccharide (LPS) treatment of mouse macrophages significantly enhanced TNFα and IL-6 production. Paroxetine treatment of macrophages, however, significantly inhibited LPS-induced IL-6 production. In contrast, paroxetine enhanced LPS-induced TNFα production in macrophages. These effects of paroxetine were mimicked by fluoxetine, another SSRI. To determine if the effects of paroxetine are mediated via modulation of the 5-HT system, we treated macrophages with 5-HT or 5-HT receptor antagonist (LY215840) in the presence of LPS and/or paroxetine. 5-HT treatment by itself did not affect LPS-induced cytokine production. LY215840, however, reversed paroxetine's effect on LPS-induced TNFα production but not IL-6. To understand the signaling mechanisms, we examined paroxetine's effect on MAPK and NFκB pathways. While paroxetine inhibited LPS-induced IκBα phosphorylation, MAPK pathways were mostly unaffected. Together these data demonstrate that paroxetine has critical but differential effects on IL-6 and TNFα production in macrophages and that it likely regulates these cytokines via distinct mechanisms.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.