ArticleThe AAPS journal2019
Impact of Interleukin-6 on Drug-Metabolizing Enzymes and Transporters in Intestinal Cells.
Article in The AAPS journal, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
15 citing papers in PubMed, 1 synthesis or guideline pooled it, 27 citations in OpenAlex.
- A systematic review on disease-drug-drug interactions with immunomodulating drugs: A critical appraisal of risk assessment and drug labelling.British journal of clinical pharmacology · 2022Pooled it
- Research progress on the chemical and pharmacological effects ofInternational journal of molecular medicine · 2026Review
- Drug-Drug Interaction Risk Assessment Strategies for Biologics in Inflammatory Bowel Disease: A Literature-Based Evidence Mini-Review.Clinical and translational science · 2026Review
- Assessment of CYP3A-mediated drug interaction via cytokine (IL-6) elevation for mosunetuzumab using physiologically-based pharmacokinetic modeling.CPT: pharmacometrics & systems pharmacology · 2024Article
- Recent Advances in Cell-Based In Vitro Models to Recreate Human Intestinal Inflammation.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Review
- PBPK Modelling of Dexamethasone in Patients With COVID-19 and Liver Disease.Frontiers in pharmacology · 2022Article
- CYP3A-status is associated with blood concentration and dose-requirement of tacrolimus in heart transplant recipients.Scientific reports · 2021Article
- Unique Regulation of Coupled NaCl Absorption by Inducible Nitric Oxide in a Spontaneous SAMP1/YitFc Mouse Model of Chronic Intestinal Inflammation.Inflammatory bowel diseases · 2021Article
- Inflammation Induces Changes in the Functional Expression of P-gp, BCRP, and MRP2: An Overview of Different Models and Consequences for Drug Disposition.Pharmaceutics · 2021Review
- Modeling Approach to Predict the Impact of Inflammation on the Pharmacokinetics of CYP2C19 and CYP3A4 Substrates.Pharmaceutical research · 2021Article
- SARS-CoV-2 infection increases tacrolimus concentrations in solid-organ transplant recipients.Clinical transplantation · 2021Article
- Human small intestinal organotypic culture model for drug permeation, inflammation, and toxicity assays.In vitro cellular & developmental biology. Animal · 2021Review
- Proinflammatory cytokines inhibit thiamin uptake by human and mouse pancreatic acinar cells: involvement of transcriptional mechanism(s).American journal of physiology. Gastrointestinal and liver physiology · 2021Article
- Inflammation is a major regulator of drug metabolizing enzymes and transporters: Consequences for the personalization of drug treatment.Pharmacology & therapeutics · 2020Review
- Metabolism of Estrogens: Turnover Differs Between Platinum-Sensitive and -Resistant High-Grade Serous Ovarian Cancer Cells.Cancers · 2020Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Inflammatory response is characterized by an increase of several cytokines. Some are known to modify drugs pharmacokinetic by reducing the expression levels of drug-metabolizing enzymes (DMEs) and transporters. This impact of inflammatory signaling is well established in hepatic cells, but not in intestinal cells. EpiIntestinal is a 3D human small intestinal tissue model with epithelial polarity, allowing good evaluation of metabolism and drug transport. This study aimed to analyze the effect of IL-6 on this tissue model. RNA sequencing was performed in cells incubated with 5, 10, or 20 ng/mL IL-6 for 8 h to 72 h to study the impact of IL-6 on drug metabolism and pharmacokinetics gene expression. The influence of IL-6 on the activity of cytochromes P450 (CYPs) was studied by measuring metabolite formation of specific substrates with LC-HRMS. Its impact on ATP-binding cassette (ABC) transport was evaluated by measuring intra- and extracellular substrates using spectrofluorometry. Exposure of EpiIntestinal cells to IL-6 resulted in reduction of some CYP mRNAs, such as CYP2C19, CYP2C9, and CYP3A4, by 40% to 50%. Activities of these CYPs were also decreased in EpiIntestinal cells by 20% to > 75%. IL-6 exposure did not modify ABCB1 and ABCCs transporter activities in this model. This study shows that gene expression levels and activities of drug-metabolizing enzymes and ABC transporters may be altered by the pro-inflammatory cytokine IL-6 in intestinal cells. If these results are confirmed in vivo, it may result in pharmacokinetic modifications, such as pre-systemic metabolism, with clinical effects, and require dosage adaptation.
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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.