ArticleHepatology (Baltimore, Md.)2015
Drug-induced allergic hepatitis develops in mice when myeloid-derived suppressor cells are depleted prior to halothane treatment.
Article in Hepatology (Baltimore, Md.), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 65 citations in OpenAlex.
- A large-scale concordance study of toxicity findings across preclinical species and humans for small molecules and biologics.Frontiers in toxicology · 2026Article
- Hepatotoxicity due to herbal dietary supplements: Past, present and the future.Food and chemical toxicology : an international journal published for the British Industrial Biological Research Association · 2022Review
- Roles of Cofactors in Drug-Induced Liver Injury: Drug Metabolism and Beyond.Drug metabolism and disposition: the biological fate of chemicals · 2022Review
- Preclinical models of idiosyncratic drug-induced liver injury (iDILI): Moving towards prediction.Acta pharmaceutica Sinica. B · 2021Review
- Idiosyncratic Drug-Induced Liver Injury: Mechanistic and Clinical Challenges.International journal of molecular sciences · 2021Review
- The hepatotoxicity of Polygonum multiflorum: The emerging role of the immune-mediated liver injury.Acta pharmacologica Sinica · 2021Review
- The Immunological Mechanisms and Immune-Based Biomarkers of Drug-Induced Liver Injury.Frontiers in pharmacology · 2021Review
- Screening for Susceptibility-Related Biomarkers of Diclofenac-Induced Liver Injury in Rats Using Metabolomics.Frontiers in pharmacology · 2021Article
- What have we learned from animal models of idiosyncratic, drug-induced liver injury?Expert opinion on drug metabolism & toxicology · 2020Review
- Animal models of drug-induced liver injury.Biochimica et biophysica acta. Molecular basis of disease · 2019Review
- Strategies for Early Prediction and Timely Recognition of Drug-Induced Liver Injury: The Case of Cyclin-Dependent Kinase 4/6 Inhibitors.Frontiers in pharmacology · 2019Review
- Editor's Highlight: An Impaired Immune Tolerance Animal Model Distinguishes the Potential of Troglitazone/Pioglitazone and Tolcapone/Entacapone to Cause IDILI.Toxicological sciences : an official journal of the Society of Toxicology · 2018Article
- Synergistic Cytotoxicity from Drugs and Cytokines In Vitro as an Approach to Classify Drugs According to Their Potential to Cause Idiosyncratic Hepatotoxicity: A Proof-of-Concept Study.The Journal of pharmacology and experimental therapeutics · 2017Article
- Drug-Induced Liver Injury: Cascade of Events Leading to Cell Death, Apoptosis or Necrosis.International journal of molecular sciences · 2017Review
- Immune mechanisms of idiosyncratic drug-induced liver injury.Journal of clinical and translational research · 2017Review
- HLA-DR7 and HLA-DQ2: Transgenic mouse strains tested as a model system for ximelagatran hepatotoxicity.PloS one · 2017Article
- Immune Modulation by Volatile Anesthetics.Anesthesiology · 2016Review
- Mechanisms of adaptation and progression in idiosyncratic drug induced liver injury, clinical implications.Liver international : official journal of the International Association for the Study of the Liver · 2016Review
- Xenobiotic and Endobiotic Mediated Interactions Between the Cytochrome P450 System and the Inflammatory Response in the Liver.Advances in pharmacology (San Diego, Calif.) · 2015Review
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13 authors at 2 institutions in 1 country.
Funding
Abstract
unlabelledClinical evidence suggests that many cases of serious idiosyncratic drug-induced liver injury are mediated by the adaptive immune system in response to hepatic drug-protein adducts, also referred to as "drug-induced allergic hepatitis"; but detailed mechanistic proof has remained elusive due to the lack of animal models. We have hypothesized that drug-induced allergic hepatitis is as rare in animals as it is in humans due at least in part to the tolerogenic nature of the liver. We provide evidence that immune tolerance can be overcome in a murine model of halothane-induced liver injury initiated by trifluoroacetylated protein adducts of halothane formed in the liver. Twenty-four hours after female Balb/cJ mice were initially treated with halothane, perivenous necrosis and an infiltration of CD11b(+) Gr-1(high) cells were observed in the liver. Further study revealed a subpopulation of myeloid-derived suppressor cells within the CD11b(+) Gr-1(high) cell fraction that inhibited the proliferation of both CD4(+) and CD8(+) T cells. When CD11b(+) Gr-1(high) cells were depleted from the liver with Gr-1 antibody treatment, enhanced liver injury was observed at 9 days after halothane rechallenge. Toxicity was associated with increased serum levels of interleukin-4 and immunoglobulins G1 and E directed against hepatic trifluoroacetylated protein adducts, as well as increased hepatic infiltration of eosinophils and CD4(+) T cells, all features of an allergic reaction. When hepatic CD4(+) T cells were depleted 5 days after halothane rechallenge, trifluoroacetylated protein adduct-specific serum immunoglobulin and hepatotoxicity were reduced.
conclusionOur data provide a rational approach for developing animal models of drug-induced allergic hepatitis mediated by the adaptive immune system and suggest that impaired liver tolerance may predispose patients to this disease.
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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.