ArticleBlood2014
Phosphoinositide 3-kinase inhibition restores neutrophil accuracy in the elderly: toward targeted treatments for immunosenescence.
Article in Blood, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 205 papers, 2 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
205 citing papers in PubMed, 2 syntheses or guidelines pooled it, 352 citations in OpenAlex.
- Smoking on the risk of acute respiratory distress syndrome: a systematic review and meta-analysis.Critical care (London, England) · 2024Pooled it
- Immunosenescence: A systems-level overview of immune cell biology and strategies for improving vaccine responses.Experimental gerontology · 2019Pooled it
- Long-acting nanoparticulate DNase-1 for effective suppression of SARS-CoV-2-mediated neutrophil activities and cytokine storm.Biomaterials · 2021Trial
- Rejuvenation of Neutrophil Functions in Association With Reduced Diabetes Risk Following Ten Weeks of Low-Volume High Intensity Interval Walking in Older Adults With Prediabetes - A Pilot Study.Frontiers in immunology · 2020Trial
- Simvastatin Improves Neutrophil Function and Clinical Outcomes in Pneumonia. A Pilot Randomized Controlled Clinical Trial.American journal of respiratory and critical care medicine · 2019Trial
- Ten weeks of high-intensity interval walk training is associated with reduced disease activity and improved innate immune function in older adults with rheumatoid arthritis: a pilot study.Arthritis research & therapy · 2018Trial
- Pulmonary Infections in the Elderly Lead to Impaired Neutrophil Targeting, Which Is Improved by Simvastatin.American journal of respiratory and critical care medicine · 2017Trial
- Neutrophil and Monocyte Bactericidal Responses to 10 Weeks of Low-Volume High-Intensity Interval or Moderate-Intensity Continuous Training in Sedentary Adults.Oxidative medicine and cellular longevity · 2017Trial
- Age-Specific Considerations in Bronchiectasis Management: Focus on Older Adults with Emphasis on Anti-inflammatory Treatment.Drugs & aging · 2026Review
- Reduced inflammatory and Th1 transcriptional profiles in geriatric versus adult cotton rats infected with respiratory syncytial virus.PLoS pathogens · 2026Article
- Immunosenescence in systemic and multi-organ aging: mechanisms, inter-organ crosstalk, and translational opportunities.npj aging · 2026Review
- Immunosenescence and cancer predisposition in pediatric transplant recipients: An emerging paradigm.World journal of transplantation · 2026Review
- Aging induces sarcopenia by disrupting the crosstalk between the skeletal muscle microenvironment and myofibers.Journal of advanced research · 2026Review
- Current Applications and Immunological Considerations ofMicroorganisms · 2026Review
- The neutrophil-to-lymphocyte ratio as a marker of immunosenescence and COVID-19 outcomes in the elderly: A narrative review.Physiological reports · 2026Review
- Altered neutrophil signalling linked to impaired chemotaxis and increased ROS and NET production in older people with frailty.Clinical and experimental immunology · 2026Article
- Age-dependent immune landscapes affect influenza vaccine effectiveness and guide precision strategies.Frontiers in immunology · 2026Review
- Transforming Growth Factor-β1 Drives Neutrophil Chemokinesis, Not Chemotaxis.Journal of inflammation research · 2026Article
- The Bacterial Swiss Army Knife: ExPEC Utilizes Multiple Resistance Mechanisms to Counteract Host Immune Responses.Vaccines · 2025Review
- Modelling the influence of vitamin D and probiotics on inflammation and the intestinal microbiota in older adults.Scientific reports · 2025Article
145 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
Abstract
Immunosenescence is the functional deterioration of the immune system during natural aging. Despite increased susceptibility to bacterial infections in older adults, age-associated changes to neutrophil responses are only partially understood, and neutrophil migration has not been characterized in detail. Here we describe reduced chemotaxis but preserved chemokinesis toward a range of inflammatory stimuli in migrating neutrophils isolated from healthy older subjects. Cross-sectional data indicate that migratory behavior changes in the sixth decade of life. Crucially, aberrant migration may increase "bystander" tissue damage and heighten inflammation as a result of excess proteinase release during inaccurate chemotaxis, as well as reducing pathogen clearance. We show evidence of increased neutrophil proteinase activity in older adults, namely, raised levels of neutrophil proteinase substrate-derived peptides and evidence of primary granule release, associated with increased systemic inflammation. Inaccurate migration was causally associated with increased constitutive phosphoinositide 3-kinase (PI3K) signaling; untreated neutrophils from old donors demonstrated significant PI3K activation compared with cells from young donors. PI3K-blocking strategies, specifically inhibition of PI3Kγ or PI3Kδ, restored neutrophil migratory accuracy, whereas SHIP1 inhibition worsened migratory flaws. Targeting PI3K signaling may therefore offer a new strategy in improving neutrophil functions during infections and reduce inappropriate inflammation in older patients.
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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.