Trial reportProceedings of the National Academy of Sciences of the United States of America2002
A molecular mechanism of action of theophylline: Induction of histone deacetylase activity to decrease inflammatory gene expression.
Trial report in Proceedings of the National Academy of Sciences of the United States of America, 2002. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 126 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
126 citing papers in PubMed, 2 syntheses or guidelines pooled it, 510 citations in OpenAlex.
- Immune and inflammatory mechanisms in asthma: insights into epigenetic modifications.Frontiers in immunology · 2025Pooled it
- Low-dose theophylline in addition to ICS therapy in COPD patients: A systematic review and meta-analysis.PloS one · 2021Pooled it
- Immune modulation in response to coffee intake: a pilot study.European journal of nutrition · 2026Trial
- Effects of Oral Doxofylline and Procaterol on Chronic Obstructive Pulmonary Disease: A Randomized Crossover Study.Medical sciences (Basel, Switzerland) · 2025Trial
- Trial
- Trial
- Effect of add-on therapy of tiotropium in COPD treated with theophylline.International journal of chronic obstructive pulmonary disease · 2008Trial
- Trial
- Theophylline Inhibits Capillary Degeneration in Early Diabetic Retinopathy.Investigative ophthalmology & visual science · 2026Article
- A green marriage: the union of theophylline's catalytic activity and healing potential.RSC advances · 2025Review
- Epigenetics-targeted drugs: current paradigms and future challenges.Signal transduction and targeted therapy · 2024Review
- HDAC6 modulates the cognitive behavioral function and hippocampal tissue pathological changes of APP/PS1 transgenic mice through HSP90-HSF1 pathway.Experimental brain research · 2024Article
- A review on current advancement in zebrafish models to study chronic inflammatory diseases and their therapeutic targets.Heliyon · 2024Review
- The Effects of Environmental Exposure on Epigenetic Modifications in Allergic Diseases.Medicina (Kaunas, Lithuania) · 2024Review
- Exploring theophylline-1,2,4-triazole tetheredFrontiers in chemistry · 2024Article
- iGEM as a human iPS cell-based global epigenetic modulation detection assay provides throughput characterization of chemicals affecting DNA methylation.Scientific reports · 2023Article
- Cryptotanshinone Reverses Corticosteroid Insensitivity by Inhibition of Phosphoinositide-3-Kinase-δ in Chronic Obstructive Pulmonary Disease.International journal of chronic obstructive pulmonary disease · 2023Article
- Application of Thermal Analysis to Evaluate Pharmaceutical Preparations Containing Theophylline.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Adenosine ABritish journal of pharmacology · 2022Review
- The association between caffeine intake and testosterone: NHANES 2013-2014.Nutrition journal · 2022Article
66 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
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The molecular mechanism for the anti-inflammatory action of theophylline is currently unknown, but low-dose theophylline is an effective add-on therapy to corticosteroids in controlling asthma. Corticosteroids act, at least in part, by recruitment of histone deacetylases (HDACs) to the site of active inflammatory gene transcription. They thereby inhibit the acetylation of core histones that is necessary for inflammatory gene transcription. We show both in vitro and in vivo that low-dose theophylline enhances HDAC activity in epithelial cells and macrophages. This increased HDAC activity is then available for corticosteroid recruitment and predicts a cooperative interaction between corticosteroids and theophylline. This mechanism occurs at therapeutic concentrations of theophylline and is dissociated from phosphodiesterase inhibition (the mechanism of bronchodilation) or the blockade of adenosine receptors, which are partially responsible for its side effects. Thus we have shown that low-dose theophylline exerts an anti-asthma effect through increasing activation of HDAC which is subsequently recruited by corticosteroids to suppress inflammatory genes.
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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.