ArticleProceedings of the National Academy of Sciences of the United States of America2016
Targeting IL-17A attenuates neonatal sepsis mortality induced by IL-18.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 110 citations in OpenAlex.
- Assessment of Serum Interleukins 18 and 22 in Predicting Neonatal Sepsis and Mortality: A Case-Control Study.Clinical medicine insights. Pediatrics · 2026Article
- The microbiome protects against septic hyperinflammation and bacterial proliferation in a zebrafish model of blood infection withFrontiers in immunology · 2026Article
- Genetic variation at the IL-18-137C>G is associated with poor sepsis prognosis and enhanced inflammatory responses: a multicenter hospital-based study.Frontiers in genetics · 2026Article
- Research Progress on Signalling Pathways Related to Sepsis-Associated Acute Kidney Injury in Children.Current issues in molecular biology · 2025Review
- Shared immune biomarkers in necrotizing enterocolitis and neonatal sepsis identified via bioinformatics and machine learning.Scientific reports · 2025Article
- Redefining the role of IL-18 in post-surgical recovery and sepsis: a key mediator of inflammation resolution.Journal of translational medicine · 2025Article
- Pyroptosis in sepsis-associated acute kidney injury: mechanisms and therapeutic perspectives.Critical care (London, England) · 2025Review
- Diagnostic utility of IL-18 plasma levels in distinguishing abdominal from non-abdominal sepsis.Frontiers in immunology · 2025Article
- Heterogeneity of Neutrophils and Immunological Function in Neonatal Sepsis: Analysis of Molecular Subtypes Based on Hypoxia-Glycolysis-Lactylation.Mediators of inflammation · 2025Article
- Modeling pathogen-driven neonatal late-onset sepsis: a modification to the murine cecal slurry.Frontiers in cellular and infection microbiology · 2025Article
- Clinical and mechanistic relevance of high-dimensionality analysis of the paediatric sepsis immunome.Frontiers in immunology · 2025Article
- Gut-derived memory γδ T17 cells exacerbate sepsis-induced acute lung injury in mice.Nature communications · 2024Article
- Host defense peptides human β defensin 2 and LL-37 ameliorate murine necrotizing enterocolitis.iScience · 2024Article
- A Novel Bifunctional Fusion Protein (Anti-IL-17A-sST2) Protects against Acute Liver Failure, Modulating the TLR4/MyD88 Pathway and NLRP3 Inflammasome Activation.Biomedicines · 2024Article
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- Neonatal Sepsis: Aetiology, Pathophysiology, Diagnostic Advances and Management Strategies.Clinical medicine insights. Pediatrics · 2024Review
- Biological and clinical roles of IL-18 in inflammatory diseases.Nature reviews. Rheumatology · 2024Review
- NLRP6 negatively regulates host defense against polymicrobial sepsis.Frontiers in immunology · 2024Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
21 authors at 7 institutions in 1 country.
Funding
Abstract
Interleukin (IL)-18 is an important effector of innate and adaptive immunity, but its expression must also be tightly regulated because it can potentiate lethal systemic inflammation and death. Healthy and septic human neonates demonstrate elevated serum concentrations of IL-18 compared with adults. Thus, we determined the contribution of IL-18 to lethality and its mechanism in a murine model of neonatal sepsis. We find that IL-18-null neonatal mice are highly protected from polymicrobial sepsis, whereas replenishing IL-18 increased lethality to sepsis or endotoxemia. Increased lethality depended on IL-1 receptor 1 (IL-1R1) signaling but not adaptive immunity. In genome-wide analyses of blood mRNA from septic human neonates, expression of the IL-17 receptor emerged as a critical regulatory node. Indeed, IL-18 administration in sepsis increased IL-17A production by murine intestinal γδT cells as well as Ly6G(+) myeloid cells, and blocking IL-17A reduced IL-18-potentiated mortality to both neonatal sepsis and endotoxemia. We conclude that IL-17A is a previously unrecognized effector of IL-18-mediated injury in neonatal sepsis and that disruption of the deleterious and tissue-destructive IL-18/IL-1/IL-17A axis represents a novel therapeutic approach to improve outcomes for human neonates with 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.