ArticleJournal of immunology (Baltimore, Md. : 1950)2010
IL-15 prevents apoptosis, reverses innate and adaptive immune dysfunction, and improves survival in sepsis.
Article in Journal of immunology (Baltimore, Md. : 1950), 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 128 papers.
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Who cites it
128 citing papers in PubMed, 218 citations in OpenAlex.
- N-terminal pro-C-natriuretic peptide and cytokine kinetics in dogs with endotoxemia.Journal of veterinary internal medicineTrial
- IL-15/NKG2D signaling-mediated activation of CD8Journal of thoracic disease · 2026Article
- Host-directed immune therapies: a second front in the battle against sepsis.The Journal of clinical investigation · 2026Review
- Cytokine-mediated, organ-specific immune modulation and dysregulation of innate lymphocytes in sepsis.Seminars in immunopathology · 2026Review
- Bench-to-Bedside Insights into the Challenges of Immunosuppression in Sepsis.Pathogens (Basel, Switzerland) · 2026Review
- The interplay between recovery and immunity in infectious and non-communicable diseases.Frontiers in cellular and infection microbiology · 2026Review
- The Dual Role of Natural Killer Cells in the Septic Liver.Journal of inflammation research · 2026Review
- Article
- A Large-Scale Single-Cell Atlas Reveals the Peripheral Immune Panorama of Bacterial Pneumonia.American journal of respiratory and critical care medicine · 2025Article
- Article
- Targeting sepsis through inflammation and oxidative metabolism.World journal of critical care medicine · 2025Review
- CD121b-positive neutrophils predict immunosuppression in septic shock.Frontiers in immunology · 2025Article
- Lymphopenia in sepsis: a narrative review.Critical care (London, England) · 2024Review
- Pretreatment with interleukin-15 attenuates inflammation and apoptosis by inhibiting NF-κB signaling in sepsis-induced myocardial dysfunction.European journal of histochemistry : EJH · 2024Article
- Assessing sepsis-induced immunosuppression to predict positive blood cultures.Frontiers in immunology · 2024Article
- Immunoadjuvant therapy in the regulation of cell death in sepsis: recent advances and future directions.Frontiers in immunology · 2024Review
- Exploring the role of antioxidants in sepsis-associated oxidative stress: a comprehensive review.Frontiers in cellular and infection microbiology · 2024Review
- Correlation Analyses Between Serum Interleukin-7, Interleukin-15 and Lactate Provide Insights Into Their Potential Roles in the Regulation of Inflammation in Elderly Septic Patients.Biomarker insights · 2024Article
- Response to: DNA transposon mechanisms and pathways of genotoxicity.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Increased Interleukin-17-Producing γδT Cells in the Brain Exacerbate the Pathogenesis of Sepsis-Associated Encephalopathy and Sepsis-Induced Anxiety in Mice.Journal of clinical medicine · 2023Article
68 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
Abstract
IL-15 is a pluripotent antiapoptotic cytokine that signals to cells of both the innate and adaptive immune system and is regarded as a highly promising immunomodulatory agent in cancer therapy. Sepsis is a lethal condition in which apoptosis-induced depletion of immune cells and subsequent immunosuppression are thought to contribute to morbidity and mortality. This study tested the ability of IL-15 to block apoptosis, prevent immunosuppression, and improve survival in sepsis. Mice were made septic using cecal ligation and puncture or Pseudomonas aeruginosa pneumonia. The experiments comprised a 2 x 2 full factorial design with surgical sepsis versus sham and IL-15 versus vehicle. In addition to survival studies, splenic cellularity, canonical markers of activation and proliferation, intracellular pro- and antiapoptotic Bcl-2 family protein expression, and markers of immune cell apoptosis were evaluated by flow cytometry. Cytokine production was examined both in plasma of treated mice and splenocytes that were stimulated ex vivo. IL-15 blocked sepsis-induced apoptosis of NK cells, dendritic cells, and CD8 T cells. IL-15 also decreased sepsis-induced gut epithelial apoptosis. IL-15 therapy increased the abundance of antiapoptotic Bcl-2 while decreasing proapoptotic Bim and PUMA. IL-15 increased both circulating IFN-gamma, as well as the percentage of NK cells that produced IFN-gamma. Finally, IL-15 increased survival in both cecal ligation and puncture and P. aeruginosa pneumonia. In conclusion, IL-15 prevents two immunopathologic hallmarks of sepsis, namely, apoptosis and immunosuppression, and improves survival in two different models of sepsis. IL-15 represents a potentially novel therapy of this highly lethal disorder.
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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.