ArticleScience translational medicine2019
Modulation of the sigma-1 receptor-IRE1 pathway is beneficial in preclinical models of inflammation and sepsis.
Article in Science translational medicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 175 papers, 8 of them syntheses 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
175 citing papers in PubMed, 8 syntheses or guidelines pooled it, 293 citations in OpenAlex.
- A systematic review and meta-analysis, investigating dose and time of fluvoxamine treatment efficacy for COVID-19 clinical deterioration, death, and Long-COVID complications.Scientific reports · 2024Pooled it
- Dextromethorphan-Bupropion for the Treatment of Depression: A Systematic Review of Efficacy and Safety in Clinical Trials.CNS drugs · 2023Pooled it
- Trial Sequential Analysis and Updated Meta-Analysis of Fluvoxamine on Clinical Deterioration in Adult Patients with Symptomatic COVID-19 Infection.International journal of environmental research and public health · 2023Pooled it
- Psychotropic drug repurposing for COVID-19: A Systematic Review and Meta-Analysis.European neuropsychopharmacology : the journal of the European College of Neuropsychopharmacology · 2023Pooled it
- Fluvoxamine for the treatment of COVID-19.The Cochrane database of systematic reviews · 2022Pooled it
- Antidepressants for COVID-19: A systematic review.Journal of affective disorders · 2022Pooled it
- Fluvoxamine for Outpatient Management of COVID-19 to Prevent Hospitalization: A Systematic Review and Meta-analysis.JAMA network open · 2022Pooled it
- The effect of antidepressants on the severity of COVID-19 in hospitalized patients: A systematic review and meta-analysis.PloS one · 2022Pooled it
- Trial
- Effect of fluvoxamine on preventing neuropsychiatric symptoms of post COVID syndrome in mild to moderate patients, a randomized placebo-controlled double-blind clinical trial.BMC infectious diseases · 2023Trial
- Effect of early treatment with fluvoxamine on risk of emergency care and hospitalisation among patients with COVID-19: the TOGETHER randomised, platform clinical trial.The Lancet. Global health · 2022Trial
- Trial
- Sigma-1 Expression in Chronic Mouse Models of Temporal Lobe Epilepsy.Molecular neurobiology · 2026Article
- Spatial architecture of immunometabolism: Mitochondrial‑organelle interfaces in immune signaling (Review).International journal of molecular medicine · 2026Review
- Targeting Neuroinflammation in Depression: The Integrative Role of Sigma-1 Receptor Modulation.Journal of neurochemistry · 2026Review
- RETREG1-Mediated Reticulophagy is Essential for Dendritic Cell Maturation and Function in Sepsis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The PVAT-MAMs Axis in Atherosclerosis: A Hypothesis-Driven Cross-Scale Conceptual Framework.International journal of molecular sciences · 2026Review
- The Sigma-1 Receptor Agonist Fluvoxamine Is Protective in Hyperglycaemia-Induced Dysfunction of Trabecular Meshwork Cells.Pharmaceuticals (Basel, Switzerland) · 2026Article
- The Acid sphingomyelinase/ceramide System in Idiopathic Inflammatory Myopathies: a Potential Treatment Target.Inflammation · 2026Review
- Fluvoxamine attenuates inflammation in experimental sepsis via novel non-canonical pathways.Inflammopharmacology · 2026Article
115 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
Sepsis is an often deadly complication of infection in which systemic inflammation damages the vasculature, leading to tissue hypoperfusion and multiple organ failure. Currently, the standard of care for sepsis is predominantly supportive, with few therapeutic options available. Because of increased sepsis incidence worldwide, there is an urgent need for discovery of novel therapeutic targets and development of new treatments. The recently discovered function of the endoplasmic reticulum (ER) in regulation of inflammation offers a potential avenue for sepsis control. Here, we identify the ER-resident protein sigma-1 receptor (S1R) as an essential inhibitor of cytokine production in a preclinical model of septic shock. Mice lacking S1R succumb quickly to hypercytokinemia induced by a sublethal challenge in two models of acute inflammation. Mechanistically, we find that S1R restricts the endonuclease activity of the ER stress sensor IRE1 and cytokine expression but does not inhibit the classical inflammatory signaling pathways. These findings could have substantial clinical implications, as we further find that fluvoxamine, an antidepressant therapeutic with high affinity for S1R, protects mice from lethal septic shock and dampens the inflammatory response in human blood leukocytes. Our data reveal the contribution of S1R to the restraint of the inflammatory response and place S1R as a possible therapeutic target to treat bacterial-derived inflammatory pathology.
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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.