ArticleJournal of leukocyte biology2014
SIRT1 inhibition during the hypoinflammatory phenotype of sepsis enhances immunity and improves outcome.
Article in Journal of leukocyte biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 97 papers, 1 of them a synthesis 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
97 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- Epigenetic mechanisms of Immune remodeling in sepsis: targeting histone modification.Cell death & disease · 2023Pooled it
- Research on Sepsis and Metabolic Reprogramming from 1998 to 2025: A Bibliometric and Visualized Analysis.Shock (Augusta, Ga.) · 2026Article
- Emerging role of SIRT1 in asthma and COPD from molecular mechanisms to translational therapy.iScience · 2026Review
- Rhynchophylline Protects Against Ischemic Injury Following Myocardial Infarction via Activation of the SIRT1/NRF2/FOXO3a Axis.Antioxidants (Basel, Switzerland) · 2026Article
- The role of the SIRT1/FOXO1 axis in regulating autophagy and inflammation in endometriosis.Journal of translational medicine · 2026Article
- SIRT2 Regulates EX VIVO PBMC Adhesion in Septic Shock Patients.Shock (Augusta, Ga.) · 2026Article
- Metabolic and post-translational modifications in sepsis-associated immune dysfunction: a conceptual framework.Frontiers in immunology · 2026Review
- Pyruvate Dehydrogenase Complex Stimulation With Dichloroacetate May Improve Septic Cardiac Dysfunction.Shock (Augusta, Ga.) · 2025Article
- The Epigenetics of Sepsis: How Gene Modulation Shapes Outcomes.Biomedicines · 2025Review
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- Exploring the role and therapeutic potential of lipid metabolism in acute kidney injury.Renal failure · 2024Review
- recAP administration ameliorates sepsis outcomes through modulation of gut and liver inflammation.Biochemical and biophysical research communications · 2024Article
- From Microcirculation to Aging-Related Diseases: A Focus on Endothelial SIRT1.Pharmaceuticals (Basel, Switzerland) · 2024Review
- TCA metabolism regulates DNA hypermethylation in LPS andProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Myricanol attenuates sepsis-induced inflammatory responses by nuclear factor erythroid 2-related factor 2 signaling and nuclear factor kappa B/mitogen-activated protein kinase pathway via upregulating Sirtuin 1.Inflammopharmacology · 2024Article
- Lonicerin promotes wound healing in diabetic rats by enhancing blood vessel regeneration through Sirt1-mediated autophagy.Acta pharmacologica Sinica · 2024Article
- Colistin Effects on Emphysematous Lung in an LPS-Sepsis Model.Antibiotics (Basel, Switzerland) · 2023Article
- Role of PFKFB3-driven glycolysis in sepsis.Annals of medicine · 2023Review
- Mitochondria in health, disease, and aging.Physiological reviews · 2023Review
- The citrus flavonoid "Nobiletin" impedes STZ-induced Alzheimer's disease in a mouse model through regulating autophagy mastered by SIRT1/FoxO3a mechanism.Inflammopharmacology · 2023Article
37 more citing papers are in PubMed but not listed here.
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
Abstract
Mechanism-based sepsis treatments are unavailable, and their incidence is rising worldwide. Deaths occur during the early acute phase of hyperinflammation or subsequent postacute hypoinflammatory phase with sustained organ failure. The acute sepsis phase shifts rapidly, and multiple attempts to treat early excessive inflammation have uniformly failed. We reported in a sepsis cell model and human sepsis blood leukocytes that nuclear NAD+ sensor SIRT1 deacetylase remodels chromatin at specific gene sets to switch the acute-phase proinflammatory response to hypoinflammatory. Importantly, SIRT1 chromatin reprogramming is reversible, suggesting that inhibition of SIRT1 might reverse postacute-phase hypoinflammation. We tested this concept in septic mice, using the highly specific SIRT1 inhibitor EX-527, a small molecule that closes the NAD+ binding site of SIRT1. Strikingly, when administered 24 h after sepsis, all treated animals survived, whereas only 40% of untreated mice survived. EX-527 treatment reversed the inability of leukocytes to adhere at the small intestine MVI, reversed in vivo endotoxin tolerance, increased leukocyte accumulation in peritoneum, and improved peritoneal bacterial clearance. Mechanistically, the SIRT1 inhibitor restored repressed endothelial E-selectin and ICAM-1 expression and PSGL-1 expression on the neutrophils. Systemic benefits of EX-527 treatment included stabilized blood pressure, improved microvascular blood flow, and a shift toward proimmune macrophages in spleen and bone marrow. Our findings reveal that modifying the SIRT1 NAD+ axis may provide a novel way to treat sepsis in its hypoinflammatory phase.
Indexed as
Identifiers
What OpenQuestion holds
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.