ArticleScience translational medicine2010
Targeting Robo4-dependent Slit signaling to survive the cytokine storm in sepsis and influenza.
Article in Science translational medicine, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 206 papers, 1 of them a synthesis 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.
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Who cites it
206 citing papers in PubMed, 1 synthesis or guideline pooled it, 330 citations in OpenAlex.
- Efficacy and Safety of Umbilical Cord-Derived Mesenchymal Stromal Cell Therapy in Preclinical Models of Sepsis: A Systematic Review and Meta-analysis.Stem cells translational medicine · 2024Pooled it
- A randomized controlled trial on the effects of goal-directed therapy on the inflammatory response open abdominal aortic aneurysm repair.Critical care (London, England) · 2015Trial
- A functional synonymous coding variant in the IL1RN gene is associated with survival in septic shock.American journal of respiratory and critical care medicine · 2014Trial
- ARF6 inhibition stabilizes the vasculature and enhances survival during endotoxic shock.Journal of immunology (Baltimore, Md. : 1950) · 2014Trial
- Pulmonary inflammation in severe pneumonia is characterised by compartmentalised and mechanistically distinct sub-phenotypes.Nature communications · 2026Article
- Artificial exosomes synergistically reshape sepsis immune homeostasis by modulating neutrophil fate and blocking PD-1/PD-L1.Cell reports. Medicine · 2026Article
- Deletion of Robo4 worsens neuroinflammation in a mouse model of Alzheimer's disease.Physiological reports · 2026Article
- Vascular Endothelial Growth Factor-D Improves Lung Vascular Integrity During Acute Lung Injury.Circulation research · 2026Article
- The immunology of sepsis: translating new insights into clinical practice.Nature reviews. Nephrology · 2026Review
- The role of aging on endothelial cell-cell junctions and pulmonary microvascular permeability in male mice.Physiological reports · 2025Article
- Unique immune and other responses of human nasal epithelial cells infected with H5N1 avian influenza virus compared to seasonal human influenza A and B viruses.Emerging microbes & infections · 2025Article
- Fluid balance after cardiac arrest: Any impact on outcome? Insights from the MIMIC IV database.Resuscitation plus · 2025Article
- Phenotypic screening in influenza-infected zebrafish identifies Nrf2-mediated compound protective against ischemia-reperfusion injury.iScience · 2025Article
- Vascular leakage during circulatory failure: physiopathology, impact and treatments.Annals of intensive care · 2025Review
- New mechanisms and therapeutic approaches to regulate vascular permeability in systemic inflammation.Current opinion in hematology · 2025Review
- CD47-amyloid-β-CD74 signaling triggers adaptive immunosuppression in sepsis.EMBO reports · 2025Article
- Review
- 4D-DIA Proteomics Uncovers New Insights into Host Salivary Response Following SARS-CoV-2 Omicron Infection.Journal of proteome research · 2025Article
- The neurorepellent SLIT2 inhibits LPS-induced proinflammatory signaling in macrophages.Journal of immunology (Baltimore, Md. : 1950) · 2025Article
- Mechanisms of the septic heart: From inflammatory response to myocardial edema.Journal of molecular and cellular cardiology · 2024Review
146 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
15 authors at 3 institutions in 1 country.
Funding
Abstract
The innate immune system provides a first line of defense against invading pathogens by releasing multiple inflammatory cytokines, such as interleukin-1beta and tumor necrosis factor-alpha, which directly combat the infectious agent and recruit additional immune responses. This exuberant cytokine release paradoxically injures the host by triggering leakage from capillaries, tissue edema, organ failure, and shock. Current medical therapies target individual pathogens with antimicrobial agents or directly either blunt or boost the host's immune system. We explored a third approach: activating with the soluble ligand Slit an endothelium-specific, Robo4-dependent signaling pathway that strengthens the vascular barrier, diminishing deleterious aspects of the host's response to the pathogen-induced cytokine storm. This approach reduced vascular permeability in the lung and other organs and increased survival in animal models of bacterial endotoxin exposure, polymicrobial sepsis, and H5N1 influenza. Thus, enhancing the resilience of the host vascular system to the host's innate immune response may provide a therapeutic strategy for treating multiple infectious agents.
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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.