ArticleShock (Augusta, Ga.)2011
Dose-dependent effect of anti-CTLA-4 on survival in sepsis.
Article in Shock (Augusta, Ga.), 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
96 citing papers in PubMed, 142 citations in OpenAlex.
- Immunology of Sepsis.Clinics in chest medicine · 2026Review
- Alveolar dysregulation of host response in pneumonia and ARDS: implications for immune modulation and infection.Annals of intensive care · 2026Review
- Hyper-inflammation and immunosuppression: redefining sepsis therapy using modern approaches.Frontiers in pharmacology · 2026Review
- T-cell dysfunction and death in sepsis: a mechanistic review.Frontiers in immunology · 2026Review
- Targeting VISTA for immunomodulation in sepsis: mechanisms and therapeutic potentials.Frontiers in immunology · 2026Review
- CXCR5-engineered mesenchymal stromal cells home to spleen and mitigate post-sepsis syndrome by preventing secondary infection.Stem cell research & therapy · 2025Article
- Immune Dysregulation in Sepsis. A Narrative Review for the Clinicians.Biomedicines · 2025Review
- Mechanisms of immune suppression in sepsis/shock: one investigator's/lab group's experience (SLB 2024 legacy award presentation).Journal of leukocyte biology · 2025Article
- The Multifaceted Role of Regulatory T Cells in Sepsis: Mechanisms, Heterogeneity, and Pathogen-Tailored Therapies.International journal of molecular sciences · 2025Review
- Case Report: Immune checkpoint inhibitor exhibits dual benefits for a refractory lymphoma patient with disseminated mucormycosis.Frontiers in medicine · 2025Article
- Reassessing sepsis research: new clues for old players and new players for an old symptom to improve patient outcomes.EXCLI journal · 2025Review
- The immunosuppressive mechanisms induced by sepsis and the corresponding treatment strategies.Frontiers in immunology · 2025Review
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- Innate immune response to Candida auris.Current opinion in microbiology · 2024Review
- mTOR Deletion Alleviates CD4+ T-Cell Dysfunction in Sepsis through Reducing CTLA4 Accumulation Mediated by Rescuing Autophagy.Mediators of inflammation · 2024Article
- CTLA-4 expression on CD4Frontiers in immunology · 2024Article
- Immunotherapy in the context of sepsis-induced immunological dysregulation.Frontiers in immunology · 2024Review
- Lactate's impact on immune cells in sepsis: unraveling the complex interplay.Frontiers in immunology · 2024Review
- Regulatory T cell homing and activation is a signature of neonatal sepsis.Frontiers in immunology · 2024Article
- CTLA-4 Checkpoint Inhibition Improves Sepsis Survival in Alcohol-Exposed Mice.ImmunoHorizons · 2024Article
36 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
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Cytotoxic T-lymphocyte antigen 4 (CTLA-4) is one of the critical inhibitory regulators of early stages of T-cell activation and proliferation, which opposes the actions of CD28-mediated costimulation. Anti-CTLA-4 therapy has been effective clinically in enhancing immunity and improving survival in patients with metastatic cancer. Sepsis is a lethal condition that shares many of the same mechanisms of immune suppression with cancer. Given the similarities in immune defects in cancer and sepsis, we examined the ability of anti-CTLA-4 antibody to block apoptosis, reverse the immunosuppression of sepsis, and improve survival in the cecal ligation and puncture model. Mice underwent sham or cecal ligation and puncture, and spleens harvested at various time points after surgery. Expression of CTLA-4 on CD4, CD8, and regulatory T cells was quantitated. Anti-CTLA-4 was administrated 6 and 24 h after surgery. Spleens were harvested at 48 h after surgery, and apoptosis and cytokine production determined. Seven-day survival studies were also conducted. Expression of CTLA-4 on CD4, CD8, and regulatory T cells increased during sepsis. Anti-CTLA-4 therapy decreased sepsis-induced apoptosis but had little effect on proinflammatory or anti-inflammatory cytokines. There was a dose-dependent effect of anti-CTLA-4 on survival. At high dose, anti-CTLA-4 worsened survival, but at lower doses, survival was significantly improved. Survival in sepsis depends on the proper balance between the proinflammatory and anti-inflammatory/immunologic systems. Anti-CTLA-4-based immunotherapy offers promise in the treatment of sepsis, but care must be used in the timing and dose of administration of the drug to prevent adverse effects.
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What OpenQuestion holds
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.