ArticleCell reports. Medicine2023
Caspase-8 inhibition improves the outcome of bacterial infections in mice by promoting neutrophil activation.
Article in Cell reports. Medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 20 citations in OpenAlex.
- Caspase-8 silences cell death-independent constitutive immune activation driven by tonic TNF-α.EMBO reports · 2026Article
- Gut-brain axis modulation by fecal microbiota transplantation improves dual-organ injury after cerebral ischemia-reperfusion via Caspase-8 dependent inhibition of necroptosis.Metabolic brain disease · 2026Article
- Enalaprilat reverses neutrophil polarization imbalance via targeting taurine-STING axis for treatment of diabetic wounds.Cell reports. Medicine · 2026Article
- Dynamic neutrophil-keratinocyte communication network centered on IL-36/TNFSF15 responses characterizes inflammatory responses in generalized pustular psoriasis.Nature communications · 2025Article
- Emerging Insights into the Interplay Between PANoptosis and Autophagy in Immune Regulation and Immune-Mediated Inflammatory Diseases.Medical sciences (Basel, Switzerland) · 2025Review
- Three-Dimensional Human Neurovascular Unit Modeling Reveals Cell-Specific Mechanisms of Traumatic Brain Injury.Journal of functional biomaterials · 2025Article
- Targeting PANoptosis: a promising therapeutic strategy for ALI/ARDS.Apoptosis : an international journal on programmed cell death · 2025Review
- Non-apoptotic caspase-8 is critical for orchestrating exaggerated inflammation during severe SARS-CoV-2 infection.Nature communications · 2025Article
- Advances inMicroorganisms · 2025Review
- Identification of biomarkers related to neutrophil extracellular traps and potential therapeutic drugs for rheumatoid arthritis using computational analysis.European journal of medical research · 2025Article
- Caspases as master regulators of programmed cell death: apoptosis, pyroptosis and beyond.Experimental & molecular medicine · 2025Review
- Targeting innate immune sensors for therapeutic strategies in infectious diseases.Journal of microbiology (Seoul, Korea) · 2025Review
- Role of endosomal toll-like receptors in immune sensing ofFrontiers in immunology · 2025Article
- Cell death in acute lung injury: caspase-regulated apoptosis, pyroptosis, necroptosis, and PANoptosis.Frontiers in pharmacology · 2025Review
- Role of the SaeRS Two-Component Regulatory System in Group BMicroorganisms · 2024Article
- Estrogen-stimulated uropathogenic E. coli mediate enhanced neutrophil responses.Scientific reports · 2024Article
- Article
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
During differentiation, neutrophils undergo a spontaneous pro-inflammatory program that is hypothesized here to be under caspase-8 control. In mice, intraperitoneal administration of the caspase-8 inhibitor z-IETD-fmk is sufficient to unleash the production of pro-inflammatory cytokines and neutrophil influx in the absence of cell death. These effects are due to selective inhibition of caspase-8 and require tonic interferon-β (IFN-β) production and RIPK3 but not MLKL, the essential downstream executioner of necroptotic cell death. In vitro, stimulation with z-IETD-fmk is sufficient to induce significant cytokine production in murine neutrophils but not in macrophages. Therapeutic administration of z-IETD-fmk improves clinical outcome in models of lethal bacterial peritonitis and pneumonia by augmenting cytokine release, neutrophil influx, and bacterial clearance. Moreover, the inhibitor protects mice against high-dose endotoxin shock. Collectively, our data unveil a RIPK3- and IFN-β-dependent pathway that is constitutively activated in neutrophils and can be harnessed therapeutically using caspase-8 inhibition.
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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.