ArticleThe Journal of experimental medicine2009
Type I interferon drives tumor necrosis factor-induced lethal shock.
Article in The Journal of experimental medicine, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
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.
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Who cites it
59 citing papers in PubMed, 82 citations in OpenAlex.
- Targeting epithelial IFN-I signaling restores barrier integrity in anti-TNF refractory Crohn's disease.Journal of Crohn's & colitis · 2026Article
- A crucial role of the malate aspartate shuttle in metabolic reprogramming in TNF-induced SIRS.Frontiers in immunology · 2025Article
- The dichotomic role of cytokines in aging.Biogerontology · 2024Review
- Paneth cell TNF signaling induces gut bacterial translocation and sepsis.Cell host & microbe · 2024Article
- Truncating NFKB1 variants cause combined NLRP3 inflammasome activation and type I interferon signaling and predispose to necrotizing fasciitis.Cell reports. Medicine · 2024Article
- Role of autoantibodies targeting interferon type 1 in COVID-19 severity: A systematic review and meta-analysis.Journal of translational autoimmunity · 2023Article
- A pharmacoproteomic landscape of organotypic intervention responses in Gram-negative sepsis.Nature communications · 2023Article
- Endothelial type I interferon response and brain diseases: identifying STING as a therapeutic target.Frontiers in cell and developmental biology · 2023Review
- Synergism of TNF-α and IFN-β triggers human airway epithelial cells death by apoptosis and pyroptosis.Molecular immunology · 2023Article
- COVID-19 diverse outcomes: Aggravated reinfection, type I interferons and antibodies.Medical hypotheses · 2022Article
- Exposing the Two Contrasting Faces of STAT2 in Inflammation.Journal of interferon & cytokine research : the official journal of the International Society for Interferon and Cytokine Research · 2022Review
- Benzyl-para-di-[5-methyl-4-(n-octylamino) pyrimidin-2(1H)one] as an interferon beta (IFN-β) modulator.Molecular diversity · 2022Article
- STING1 in sepsis: Mechanisms, functions, and implications.Chinese journal of traumatology = Zhonghua chuang shang za zhi · 2022Review
- TRIMs: selective recruitment at different steps of the NF-κB pathway-determinant of activation or resolution of inflammation.Cellular and molecular life sciences : CMLS · 2021Review
- A Kinetic Response Model for Standardized Regression Analyses of Inflammation-Triggered Hypothermic Body Temperature-Time Courses in Mice.Frontiers in physiology · 2021Article
- Polymorphonuclear Cells Show Features of Dysfunctional Activation During Fatal Sepsis.Frontiers in immunology · 2021Article
- RIG-I and TLR4 responses and adverse outcomes in pediatric influenza-related critical illness.The Journal of allergy and clinical immunology · 2020Observational
- ZBP1 mediates interferon-induced necroptosis.Cellular & molecular immunology · 2020Article
- Production of IFNβ by Conventional Dendritic Cells after Stimulation with Viral Compounds and IFNβ-Independent IFNAR1-Signaling Pathways are Associated with Aggravation of Polymicrobial Sepsis.International journal of molecular sciences · 2019Article
- Review
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Tumor necrosis factor (TNF) is reputed to have very powerful antitumor effects, but it is also a strong proinflammatory cytokine. Injection of TNF in humans and mice leads to a systemic inflammatory response syndrome with major effects on liver and bowels. TNF is also a central mediator in several inflammatory diseases. We report that type I interferons (IFNs) are essential mediators of the lethal response to TNF. Mice deficient in the IFN-alpha receptor 1 (IFNAR-1) or in IFN-beta are remarkably resistant to TNF-induced hypothermia and death. After TNF injection, IFNAR-1(-/-) mice produced less IL-6, had less bowel damage, and had less apoptosis of enterocytes and hepatocytes compared with wild-type (WT) mice. Extensive gene expression analysis in livers of WT and IFNAR-1(-/-) mice revealed a large deficiency in the response to TNF in the knockout mice, especially of IFN-stimulated response element-dependent genes, many of which encode chemokines. In livers of IFNAR-1(-/-) mice, fewer infiltrating white blood cells (WBCs) were detected by immunohistochemistry. Deficiency of type I IFN signaling provided sufficient protection for potentially safer therapeutic use of TNF in tumor-bearing mice. Our data illustrate that type I IFNs act as essential mediators in TNF-induced lethal inflammatory shock, possibly by enhancing cell death and inducing chemokines and WBC infiltration in tissues.
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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.