ArticleJournal of leukocyte biology2009
Alpha-1-antitrypsin is an endogenous inhibitor of proinflammatory cytokine production in whole blood.
Article in Journal of leukocyte biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT07125664 (A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations), which is not on this map. Cited by 103 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.
A Two-center, Randomized, Double-blind, Placebo-controlled Study of Intravenous Plasma-purified Alpha-1 Antitrypsin for Hospitalized Patients With COPD Exacerbations (AECOPD Study)
Who cites it
103 citing papers in PubMed, 179 citations in OpenAlex.
- Elevated alpha-1 antitrypsin and C-reactive protein: association on all-cause and cause-specific mortality in older adults.GeroScience · 2026Trial
- A randomized, double-blind, placebo-controlled trial of intravenous alpha-1 antitrypsin for ARDS secondary to COVID-19.Med (New York, N.Y.) · 2022Trial
- A Phase II, Double-Blind, Randomized, Placebo-Controlled, Multicenter Study Evaluating the Efficacy and Safety of Alpha-1 Antitrypsin (AAT) (GlassiaInternational journal of molecular sciences · 2019Trial
- The Biological Effects of Double-Dose Alpha-1 Antitrypsin Augmentation Therapy. A Pilot Clinical Trial.American journal of respiratory and critical care medicine · 2019Trial
- αBlood · 2018Trial
- Polymeric alpha-1 antitrypsin perturbs Paneth cell proteostasis and exacerbates intestinal inflammation.Signal transduction and targeted therapy · 2026Article
- Human α1-Antitrypsin Inhibits Nociceptor Excitability and Relieves Inflammatory and Neuropathic Pain.Biomolecules · 2026Article
- Alpha-1 antitrypsin as a new biomarker of inflammation, infection and disease severity in community-acquired pneumonia: a prospective cohort study.Scientific reports · 2026Article
- The Role of Alpha-1 Antitrypsin in the Pathophysiology and Treatment of Inflammatory Lung Diseases.Journal of inflammation research · 2026Review
- Mass Spectrometry-Based Comparative Analysis ofACS chemical neuroscience · 2025Article
- Role of Transcription Factor, LIM Homeobox 9 (LHX9) in Inflammatory Response by PGE2 and Thrombin in SERPINA1-Silencing Endometrial Stromal Cells.Molecular reproduction and development · 2025Article
- Assessing inflammatory protein biomarkers in COPD subjects with and without alpha-1 antitrypsin deficiency.Respiratory research · 2025Article
- Review
- Graft-Versus-Host Disease Mouse Models: A Clinical-Translational Perspective.Methods in molecular biology (Clifton, N.J.) · 2025Review
- Impact of Hypoxia on Neutrophil Degranulation and Inflammatory Response in Alpha-1 Antitrypsin Deficiency Patients.Antioxidants (Basel, Switzerland) · 2024Article
- SerpinA1 levels in amyotrophic lateral sclerosis patients: An exploratory study.European journal of neurology · 2024Article
- Aerobic Exercise Improves the Overall Outcome of Type 2 Diabetes Mellitus Among People With Mental Disorders.Depression and anxiety · 2024Review
- Activities and concentration of alpha-1 antitrypsin and cystatin C in serum from patients with house dust mite asthma.Asia Pacific allergy · 2023Article
- Impact of the COVID-19 pandemic on well-being and quality of life of patients with alpha-1-antitrypsin deficiency.Respiratory research · 2023Article
- Inflammation-Involved Proteins in Blood Serum of Cataract Patients-A Preliminary Study.Biomedicines · 2023Article
43 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
4 authors at 2 institutions in 1 country.
Funding
Abstract
Several observations suggest endogenous suppressors of inflammatory mediators are present in human blood. alpha-1-Antitrypsin (AAT) is the most abundant serine protease inhibitor in blood, and AAT possesses anti-inflammatory activity in vitro and in vivo. Here, we show that in vitro stimulation of whole blood from persons with a genetic AAT deficiency resulted in enhanced cytokine production compared with blood from healthy subjects. Using whole blood from healthy subjects, dilution of blood with RPMI tissue-culture medium, followed by incubation for 18 h, increased spontaneous production of IL-8, TNF-alpha, IL-1 beta, and IL-1R antagonist (IL-1Ra) significantly, compared with undiluted blood. Dilution-induced cytokine production suggested the presence of one or more circulating inhibitors of cytokine synthesis present in blood. Serially diluting blood with tissue-culture medium in the presence of cytokine stimulation with heat-killed Staphylococcus epidermidis (S. epi) resulted in 1.2- to 55-fold increases in cytokine production compared with S. epi stimulation alone. Diluting blood with autologous plasma did not increase the production of IL-8, TNF-alpha, IL-1 beta, or IL-1Ra, suggesting that the endogenous, inhibitory activity of blood resided in plasma. In whole blood, diluted and stimulated with S. epi, exogenous AAT inhibited IL-8, IL-6, TNF-alpha, and IL-1 beta significantly but did not suppress induction of the anti-inflammatory cytokines IL-1Ra and IL-10. These ex vivo and in vitro observations suggest that endogenous AAT in blood contributes to the suppression of proinflammatory cytokine synthesis.
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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.