ArticleBritish journal of pharmacology2014
Targeted inhibition of IL-18 attenuates irinotecan-induced intestinal mucositis in mice.
Article in British journal of pharmacology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 48 citations in OpenAlex.
- Interleukin-18 armours antitumour immune effectors.Nature reviews. Immunology · 2026Review
- The Anthocyanidins Malvidin and Cyanidin Alleviate Irinotecan-Triggered Intestinal Mucositis by Modulating Oxidative Stress and Cytokine Release.International journal of molecular sciences · 2025Article
- Is There an Interplay between Environmental Factors, Microbiota Imbalance, and Cancer Chemotherapy-Associated Intestinal Mucositis?Pharmaceuticals (Basel, Switzerland) · 2024Article
- Released dsDNA-triggered inflammasomes serve as intestinal radioprotective targets.Clinical & translational immunology · 2023Article
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Chronic Morphine Induces IL-18 in Ileum Myenteric Plexus Neurons Through Mu-opioid Receptor Activation in Cholinergic and VIPergic Neurons.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2022Article
- Dioscin Alleviates Cisplatin-Induced Mucositis in Rats by Modulating Gut Microbiota, Enhancing Intestinal Barrier Function and Attenuating TLR4/NF-κB Signaling Cascade.International journal of molecular sciences · 2022Article
- Review
- IL-33 and IL-18 in Inflammatory Bowel Disease Etiology and Microbial Interactions.Frontiers in immunology · 2019Review
- CPT-11-Induced Delayed Diarrhea Develops via Reduced Aquaporin-3 Expression in the Colon.International journal of molecular sciences · 2018Article
- Telmisartan Modulates the Oral Mucositis Induced by 5-Fluorouracil in Hamsters.Frontiers in physiology · 2018Article
- Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation.Cell research · 2017Article
- The involvement of mast cells in the irinotecan-induced enteric neurons loss and reactive gliosis.Journal of neuroinflammation · 2017Article
- Intestinal permeability to iohexol as an in vivo marker of chemotherapy-induced gastrointestinal toxicity in Sprague-Dawley rats.Cancer chemotherapy and pharmacology · 2016Article
- Irinotecan (CPT-11)-induced elevation of bile acids potentiates suppression of IL-10 expression.Toxicology and applied pharmacology · 2016Article
- Interleukin-18 as a target for modulation of irinotecan-induced intestinal toxicity: a step towards a better therapeutic index?: Commentary on Lima-Junior et al., Br J Pharmacol 171: 2335-2350.British journal of pharmacology · 2015Article
- The Adaptor Protein Myd88 Is a Key Signaling Molecule in the Pathogenesis of Irinotecan-Induced Intestinal Mucositis.PloS one · 2015Article
- Diarrhea Induced by Small Molecule Tyrosine Kinase Inhibitors Compared With Chemotherapy: Potential Role of the Microbiome.Integrative cancer therapiesReview
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Authors and funding
13 authors at 4 institutions in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
background and purposeIntestinal mucositis is a common side-effect of irinotecan-based cancer chemotherapy regimens. This mucositis is associated with cytokine activation and NO synthesis. Production of IL-18 is up-regulated in patients suffering from inflammatory bowel disease. Therefore, we have investigated the role of IL-18 in the pathogenesis of irinotecan-induced intestinal mucositis. EXPERIMENTAL APPROACH: Wild type (WT), IL-18 or caspase-1 knockout mice were treated with either saline or irinotecan (60 mg·kg⁻¹ per 4 days, i.p.) or the IL-18 binding protein (IL-18bp, 10 mg·kg⁻¹) before irinotecan. On day 5, diarrhoea was monitored and proximal intestinal strips were obtained for histopathology, in vitro gut contractility, myeloperoxidase (MPO) and inducible NOS (iNOS) activity, and detection of IL-18 expression. KEY
resultsIrinotecan induced severe diarrhoea accompanied by intestinal injury (villi shortening and increased crypt depth). Additionally, irinotecan treatment increased MPO and iNOS activity, iNOS immunostaining and IL-18 expression in WT mice compared with saline treatment. The IL-18 production was associated with macrophages. In vitro, intestinal smooth muscle strips were hyperresponsive to ACh after irinotecan treatment. Increases in MPO and iNOS activity, intestinal contractility and diarrhoea were prevented in caspase-1 knockout and IL-18 knockout mice, and in IL-18bp-treated WT mice. Furthermore, the Survival of irinotecan-treated mice was increased and iNOS immunoexpression and IL-18 production prevented in IL-18 knockout mice. CONCLUSIONS AND IMPLICATIONS: Targeting IL-18 function may be a promising therapeutic approach to decreasing the severity of intestinal mucositis during irinotecan treatment regimens.
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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.