ArticlePloS one2013
Roflumilast inhibits lipopolysaccharide-induced tumor necrosis factor-α and chemokine production by human lung parenchyma.
Article in PloS one, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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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.
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Who cites it
15 citing papers in PubMed, 27 citations in OpenAlex.
- Safety, pharmacokinetics, and pharmacodynamics of ART-648, a PDE4 inhibitor in healthy subjects: A randomized, placebo-controlled phase I study.Clinical and translational science · 2024Trial
- Characterization of LY2775240, a selective phosphodiesterase-4 inhibitor, in nonclinical models and in healthy subjects.Clinical and translational science · 2021Trial
- Differences in the Inflammatory Response and Corticoid Responsiveness of Human Lung Macrophages and Parenchymal Explants Exposed to Cigarette Smoke Extracts.Basic & clinical pharmacology & toxicology · 2025Article
- Integrating TNF-α with Established Tumor Markers to Enhance Prognostic Accuracy in Gastric Cancer: A Prospective Observational Study.Biomedicines · 2025Article
- Plasma Levels of CXCL9 and MCP-3 are Increased in Asthma-COPD Overlap (ACO) Patients.International journal of chronic obstructive pulmonary disease · 2025Article
- Scope of adjuvant therapy using roflumilast, a PDE-4 inhibitor against COVID-19.Pulmonary pharmacology & therapeutics · 2021Review
- Adiponectin Inhibits the Production of TNF-α, IL-6 and Chemokines by Human Lung Macrophages.Frontiers in pharmacology · 2021Article
- Phosphodiesterase-4 Inhibitors for Non-COPD Respiratory Diseases.Frontiers in pharmacology · 2021Review
- Chloroquine Inhibits the Release of Inflammatory Cytokines by Human Lung Explants.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2020Article
- Clinical Relevance of the Anti-inflammatory Effects of Roflumilast on Human Bronchus: Potentiation by a Long-Acting Beta-2-Agonist.Frontiers in pharmacology · 2020Article
- Lung Macrophage Phenotypes and Functional Responses: Role in the Pathogenesis of COPD.International journal of molecular sciences · 2018Review
- Human lung and monocyte-derived macrophages differ with regard to the effects of βRespiratory research · 2017Article
- Roles of roflumilast, a selective phosphodiesterase 4 inhibitor, in airway diseases.Journal of thoracic disease · 2017Review
- Roflumilast: A Review in COPD.Drugs · 2015Review
- The long-acting β2 -adrenoceptor agonist olodaterol attenuates pulmonary inflammation.British journal of pharmacology · 2015Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRoflumilast is the first phosphodiesterase-4 (PDE4) inhibitor to have been approved for the treatment of COPD. The anti-inflammatory profile of PDE4 inhibitors has not yet been explored in human lung tissues. We investigated the effects of roflumilast and its active metabolite roflumilast-N-oxide on the lipopolysaccharide (LPS)-induced release of tumor necrosis factor-alpha (TNF-α) and chemokines by human lung parenchymal explants. We also investigated roflumilast's interaction with the long-acting β2-agonist formoterol.
methodsExplants from 25 patients undergoing surgical lung resection were incubated with Roflumilast, Roflumilast-N-oxide and formoterol and stimulated with LPS. Levels of TNF-α, chemokines (in the culture supernatants) and cyclic adenosine monophosphate (in tissue homogenates) were determined with appropriate immunoassays.
resultsRoflumilast and Roflumilast-N-oxide concentration-dependently reduced the release of TNF-α and chemokines CCL2, CCL3, CCL4, CXCL9 and CXCL10 from LPS-stimulated human lung explants, whereas CXCL1, CXCL5 and CXCL8 release was not altered. Formoterol (10 nM) partially decreased the release of the same cytokines and significantly increased the inhibitory effect of roflumilast on the release of the cytokines.
conclusionsIn human lung parenchymal explants, roflumilast and roflumilast-N-oxide reduced the LPS-induced release of TNF-α and chemokines involved in the recruitment of monocytes and T-cells but not those involved in the recruitment of neutrophils. Addition of formoterol to roflumilast provided superior in vitro anti-inflammatory activity, which may translate into greater efficacy in COPD.
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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.