ArticleCell death & disease2016
Proton pump inhibitors protect mice from acute systemic inflammation and induce long-term cross-tolerance.
Article in Cell death & disease, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03452865 (Proton Pump Inhibitors), which is not on this map. Cited by 25 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Proton Pump Inhibitors (PPI) as a New Strategy for Therapy in Sepsis: Clinical Trial to Reduce Severity of Organ Failure and in Vitro Experiments to Search Specific Hallmarks in Monocytes From Septic Patients and to Characterize the Mechanism of Action of PPI
Who cites it
25 citing papers in PubMed, 2 syntheses or guidelines pooled it, 44 citations in OpenAlex.
- Proton pump inhibitor effect on macrophage and neutrophil function: a systematic review.Frontiers in immunology · 2024Pooled it
- Effectiveness of Proton-Pump Inhibitors in Chronic Obstructive Pulmonary Disease: A Meta-Analysis of Randomized Controlled Trials.Frontiers in medicine · 2022Pooled it
- Comparative randomized trial evaluating the effect of proton pump inhibitor versus histamine 2 receptor antagonist as an adjuvant therapy in diffuse large B-cell lymphoma.Medical oncology (Northwood, London, England) · 2021Trial
- Comparison of the anti-inflammatory effects of esomeprazole and fexuprazan in lipopolysaccharide-stimulated RAW 264.7 macrophages.BMC pharmacology & toxicology · 2026Article
- The long-term effect of metabolic bariatric surgery on innate immune cell phenotype and function.International journal of obesity (2005) · 2025Observational
- Long-Term Humoral Response to Hepatitis B Vaccination in Patients with Inflammatory Bowel Disease in Oman: Impact of Prednisolone and Esomeprazole as Contributing Factors.Oman medical journal · 2025Article
- Proton pump inhibitors reduce survival outcomes in patients treated with capecitabine: meta-analysis.Ecancermedicalscience · 2025Review
- Long-term administration of omeprazole in mice: a study of behavior, inflammatory, and oxidative stress alterations with focus on central nervous system.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- A retrospective analysis of clinical outcomes between hospitalized patients with COVID-19 who received famotidine or pantoprazole.JGH open : an open access journal of gastroenterology and hepatology · 2023Article
- NLRP3 inhibition improves maternal hypertension, inflammation, and vascular dysfunction in response to placental ischemia.American journal of physiology. Regulatory, integrative and comparative physiology · 2023Article
- Spontaneous NLRP3 inflammasome-driven IL-1-β secretion is induced in severe COVID-19 patients and responds to anakinra treatment.The Journal of allergy and clinical immunology · 2022Article
- Perinatal derivatives: How to best validate their immunomodulatory functions.Frontiers in bioengineering and biotechnology · 2022Review
- Candidate Drugs Screening for Behcet's Disease Based on Bioinformatics Analysis and Mouse Experiments.Frontiers in immunology · 2022Article
- Improved motility in the gastrointestinal tract of a postoperative ileus rat model with ilaprazole.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2021Article
- Use of omeprazole, the proton pump inhibitor, as a potential therapy for the capecitabine-induced hand-foot syndrome.Scientific reports · 2021Article
- Article
- Omeprazole inhibits IgE-mediated mast cell activation and allergic inflammation induced by ingested allergen in mice.The Journal of allergy and clinical immunology · 2020Article
- Neutrophil heterogeneity and fate in inflamed tissues: implications for the resolution of inflammation.American journal of physiology. Cell physiology · 2020Article
- Profiling and Identification of Omeprazole Metabolites in Mouse Brain and Plasma by Isotope Ratio-Monitoring Liquid Chromatography-Mass Spectrometric Method.Life (Basel, Switzerland) · 2020Article
- Pharmacological Effects and Toxicogenetic Impacts of Omeprazole: Genomic Instability and Cancer.Oxidative medicine and cellular longevity · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Incidence of sepsis is increasing, representing a tremendous burden for health-care systems. Death in acute sepsis is attributed to hyperinflammatory responses, but the underlying mechanisms are still unclear. We report here that proton pump inhibitors (PPIs), which block gastric acid secretion, selectively inhibited tumor necrosis factor-α (TNF-α) and interleukin-1β (IL-1β) secretion by Toll-like receptor (TLR)-activated human monocytes in vitro, in the absence of toxic effects. Remarkably, the oversecretion of IL-1β that represents a hallmark of monocytes from patients affected by cryopyrin-associated periodic syndrome is also blocked. Based on these propaedeutic experiments, we tested the effects of high doses of PPIs in vivo in the mouse model of endotoxic shock. Our data show that a single administration of PPI protected mice from death (60% survival versus 5% of untreated mice) and decreased TNF-α and IL-1β systemic production. PPIs were efficacious even when administered after lipopolysaccharide (LPS) injection. PPI-treated mice that survived developed a long-term cross-tolerance, becoming resistant to LPS- and zymosan-induced sepsis. In vitro, their macrophages displayed impaired TNF-α and IL-1β to different TLR ligands. PPIs also prevented sodium thioglycollate-induced peritoneal inflammation, indicating their efficacy also in a non-infectious setting independent of TLR stimulation. Lack of toxicity and therapeutic effectiveness make PPIs promising new drugs against sepsis and other severe inflammatory conditions.
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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.