ArticleProceedings of the National Academy of Sciences of the United States of America2004
Reversing established sepsis with antagonists of endogenous high-mobility group box 1.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 509 papers, 2 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
509 citing papers in PubMed, 2 syntheses or guidelines pooled it, 1,124 citations in OpenAlex.
- Elevated HMGB1 Levels in Neonates With Bronchopulmonary Dysplasia: A Systematic Review and Meta-Analysis.Canadian respiratory journal · 2026Pooled it
- HMGB1: an overview of its versatile roles in the pathogenesis of colorectal cancer.Cellular oncology (Dordrecht, Netherlands) · 2020Pooled it
- RAGE Signalling in Acute Inflammatory Disorders: Therapeutic Potential of Natural Products.Biomolecules · 2026Review
- Sleep interruption aggravates sepsis by rewiring the macrophage immune response.Journal of immunology (Baltimore, Md. : 1950) · 2026Article
- Macrophage metabolism reprogramming in sepsis: Pathogenesis and therapeutic implications (Review).International journal of molecular medicine · 2026Review
- HMGB1-Platelet Interactions: Mechanisms and Targeted Therapy Strategies.Thrombosis and haemostasis · 2026Review
- Lipopolysaccharide and HMGB1: key regulatory factors in the pathophysiology of sepsis a mechanistic and therapeutic review.Frontiers in immunology · 2026Review
- A comparative analysis of HMGB1 and pCTS-L immunomodulatory properties in human peripheral blood mononuclear cells.Frontiers in immunology · 2026Article
- Pharmacological intervention of the HMGB1-pCTS-L axis to ameliorate inflammatory diseases.Frontiers in immunology · 2026Review
- HMGB1 and metabolic pathways in Acinetobacter baumannii pneumonia: an associative study.BMC infectious diseases · 2025Article
- Salivary and serum levels of high mobility group box protein 1 in periodontitis: a cross-sectional observational study.BMC oral health · 2025Observational
- Repurposing a Detrimental Antibody Epitope as Targeted Therapeutics for Sepsis and Rheumatoid Arthritis.Research square · 2025Article
- Anti-HMGB1 Antibody Therapy Ameliorates Spinal Cord Ischemia-Reperfusion Injury in Rabbits.International journal of molecular sciences · 2025Article
- HMGB1 as an emerging key modulator of bone remodeling: a narrative review.Stem cell research & therapy · 2025Review
- Article
- Targeting high-mobility-group-box-1-mediated inflammation: a promising therapeutic approach for myocardial infarction.Inflammopharmacology · 2025Review
- HMGB1 in Septic Muscle Atrophy: Roles and Therapeutic Potential for Muscle Atrophy and Regeneration.Journal of cachexia, sarcopenia and muscle · 2025Review
- Serial cerebrospinal fluid concentrations of high mobility group box 1 in bacterial meningitis: a retrospective cohort study.BMC infectious diseases · 2025Article
- [Nafamostat Mesylate Alleviates Renal Ischemia-Reperfusion Injury in a Rat Model Through HMGB1 Modulation: An Omics Analysis -Based Study of the Protective Effect and the Mechanisms Involved].Sichuan da xue xue bao. Yi xue ban = Journal of Sichuan University. Medical science edition · 2025Article
- Roles of the Receptor for Advanced Glycation End Products and Its Ligands in the Pathogenesis of Alzheimer's Disease.International journal of molecular sciences · 2025Review
449 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
18 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Despite significant advances in intensive care therapy and antibiotics, severe sepsis accounts for 9% of all deaths in the United States annually. The pathological sequelae of sepsis are characterized by a systemic inflammatory response, but experimental therapeutics that target specific early inflammatory mediators [tumor necrosis factor (TNF) and IL-1beta] have not proven efficacious in the clinic. We recently identified high mobility group box 1 (HMGB1) as a late mediator of endotoxin-induced lethality that exhibits significantly delayed kinetics relative to TNF and IL-1beta. Here, we report that serum HMGB1 levels are increased significantly in a standardized model of murine sepsis, beginning 18 h after surgical induction of peritonitis. Specific inhibition of HMGB1 activity [with either anti-HMGB1 antibody (600 microg per mouse) or the DNA-binding A box (600 microg per mouse)] beginning as late as 24 h after surgical induction of peritonitis significantly increased survival (nonimmune IgG-treated controls = 28% vs. anti-HMGB1 antibody group = 72%, P < 0.03; GST control protein = 28% vs. A box = 68%, P < 0.03). Animals treated with either HMGB1 antagonist were protected against the development of organ injury, as evidenced by improved levels of serum creatinine and blood urea nitrogen. These observations demonstrate that specific inhibition of endogenous HMGB1 therapeutically reverses lethality of established sepsis indicating that HMGB1 inhibitors can be administered in a clinically relevant time frame.
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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.