ArticleCritical care (London, England)2023
Therapeutic S100A8/A9 blockade inhibits myocardial and systemic inflammation and mitigates sepsis-induced myocardial dysfunction.
Article in Critical care (London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 51 papers.
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51 citing papers in PubMed, 83 citations in OpenAlex.
- Upregulation of S100A8/A9 Potentiates Radiation-Induced Intestinal Injury via MAPK and NF-κB Signaling Pathways.Advances in radiation oncology · 2026Article
- Exploring the mechanism of polymorphonuclear neutrophils against sepsis based on immune model.Annals of medicine · 2026Review
- Restricted TCR Diversity and Expansion of CD177MedComm · 2026Article
- S100A9 modulates USP7-mediated stabilization of NCOA4 to promote ferroptosis in sepsis-associated acute lung injury.Redox biology · 2026Article
- Cross-species comparative spatial transcriptomics of hair follicle-T cell interactions identifies conserved drivers of cutaneous lupus erythematosus skin disease and associated hair loss.Nature communications · 2026Article
- Article
- S100A9 lactylation facilitated sepsis-related acute respiratory distress syndrome via promoting transcription activation of IL-1β in macrophages.Cell communication and signaling : CCS · 2026Article
- Transcriptomic insights into the co-occurring psychological symptoms and cardiovascular risks among military service members and veterans with mild traumatic brain injury: A LIMBIC-CENC study.Brain, behavior, & immunity - health · 2026Article
- Amphiregulin attenuates sepsis-induced myocardial dysfunction by maintaining the localization of connexin43.Inflammation and regeneration · 2026Article
- Plasma proteomics identifies S100A8/A9 as a novel biomarker and therapeutic target for fulminant myocarditis.Journal of advanced research · 2026Article
- Prostaglandins prevent long-lasting pain in a mouse model of chronic postsurgical pain.British journal of anaesthesia · 2026Article
- Serum Calprotectin in Hospitalized Patients with COVID-19 in Relation to High-Dimensional Serum Proteomic Patterns.International journal of molecular sciences · 2026Observational
- The S100A8/A9-NETosis feedback loop in sepsis: potential mechanisms, immune crosstalk, and therapeutic targeting.Frontiers in immunology · 2026Review
- Article
- S100A8/A9 Inhibition Reduces Neutrophil Extracellular Trap Formation and Mitigates Sepsis-Related Liver Injury.Journal of inflammation research · 2026Article
- Targeting S100A8/A9: a molecular gateway to oral inflammation, microglial activation and neuroinflammation.Frontiers in immunology · 2026Review
- Identification and validation of key genes related to apoptosis in multiple organ dysfunction syndrome.European journal of medical research · 2025Article
- Calprotectin, Azurocidin, and Interleukin-8: Neutrophil Signatures with Diagnostic and Prognostic Value in Sepsis.Biomedicines · 2025Article
- Exploring the Relevance of S100A8 and S100A9 Proteins in Preeclampsia: A Narrative Review.International journal of molecular sciences · 2025Review
- Neural stem cell-delivered oncolytic virus via intracerebroventricular administration enhances glioblastoma therapy and immune modulation.Journal for immunotherapy of cancer · 2025Article
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Authors and funding
15 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
BACKGROUND AND
aimsThe triggering factors of sepsis-induced myocardial dysfunction (SIMD) are poorly understood and are not addressed by current treatments. S100A8/A9 is a pro-inflammatory alarmin abundantly secreted by activated neutrophils during infection and inflammation. We investigated the efficacy of S100A8/A9 blockade as a potential new treatment in SIMD.
methodsThe relationship between plasma S100A8/A9 and cardiac dysfunction was assessed in a cohort of 62 patients with severe sepsis admitted to the intensive care unit of Linköping University Hospital, Sweden. We used S100A8/A9 blockade with the small-molecule inhibitor ABR-238901 and S100A9
resultsIn sepsis patients, elevated plasma S100A8/A9 was associated with left-ventricular (LV) systolic dysfunction and increased SOFA score. In wild-type mice, 5 mg/kg of bacterial lipopolysaccharide (LPS) induced rapid plasma S100A8/A9 increase and acute LV dysfunction. Two ABR-238901 doses (30 mg/kg) administered intraperitoneally with a 6 h interval, starting directly after LPS or at a later time-point when LV dysfunction is fully established, efficiently prevented and reversed the phenotype, respectively. In contrast, dexamethasone did not improve cardiac function compared to PBS-treated endotoxemic controls. S100A8/A9 inhibition potently reduced systemic levels of inflammatory mediators, prevented upregulation of inflammatory genes and restored mitochondrial function in the myocardium. The S100A9
conclusionElevated S100A8/A9 is associated with the development of LV dysfunction in severe sepsis patients and in a mouse model of endotoxemia. Pharmacological blockade of S100A8/A9 with ABR-238901 has potent anti-inflammatory effects, mitigates myocardial dysfunction and might represent a novel therapeutic strategy for patients with severe sepsis.
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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.