Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model
<b>Background/Objectives</b>: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and refere...
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2025-06-01
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| author | Emese Ritter Kitti Hohl László Kereskai Ágnes Kemény Dóra Hargitai Veronika Szombati Anikó Perkecz Eszter Pakai Andras Garami Ákos Zsembery Zsuzsanna Helyes Kata Csekő |
| author_facet | Emese Ritter Kitti Hohl László Kereskai Ágnes Kemény Dóra Hargitai Veronika Szombati Anikó Perkecz Eszter Pakai Andras Garami Ákos Zsembery Zsuzsanna Helyes Kata Csekő |
| author_sort | Emese Ritter |
| collection | DOAJ |
| description | <b>Background/Objectives</b>: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. <b>Methods</b>: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; <i>E. coli</i> O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. <b>Results</b>: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. <b>Conclusions</b>: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents. |
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| language | English |
| publishDate | 2025-06-01 |
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| spelling | doaj-art-0f208a4c6bc84ec4b4a86d43c3f30b162025-06-25T13:32:15ZengMDPI AGBiomedicines2227-90592025-06-01136149810.3390/biomedicines13061498Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse ModelEmese Ritter0Kitti Hohl1László Kereskai2Ágnes Kemény3Dóra Hargitai4Veronika Szombati5Anikó Perkecz6Eszter Pakai7Andras Garami8Ákos Zsembery9Zsuzsanna Helyes10Kata Csekő11Department of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pathology, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pathology, Forensic and Insurance Medicine, Faculty of Medicine, Semmelweis University, Üllői út 93, H-1091 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Thermophysiology, Institute for Translational Medicine, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Oral Biology, Faculty of Dentistry, Semmelweis University, Nagyvárad tér 4, H-1089 Budapest, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, HungaryDepartment of Pharmacology and Pharmacotherapy, Medical School, University of Pécs, Szigeti út 12, H-7624 Pécs, Hungary<b>Background/Objectives</b>: In preclinical research of airway inflammation, the endotoxin (lipopolysaccharide: LPS)–induced acute interstitial pneumonitis is the most commonly used mechanism model. However, studies apply different LPS serotypes, doses, administration routes, and reference compounds, making result interpretation challenging and drawing conclusions difficult. Therefore, here we aimed to optimize, characterize, and validate this model with dexamethasone in mice. <b>Methods</b>: Pneumonitis was induced by intratracheal LPS (0.25, 1, 2.5, 5 mg/kg; <i>E. coli</i> O111:B4) in C57BL/6J and NMRI mice; controls received phosphate-buffered saline (PBS). Dexamethasone (5 mg/kg i.p.) was used as a positive control. Respiratory functions were measured by restrained plethysmography 24 h after induction, and core body temperature was monitored. Lungs were excised and weighed, and then myeloperoxidase (MPO) activity and histopathological analysis were performed to assess pulmonary inflammation. <b>Results</b>: LPS-induced significant body weight loss, perivascular pulmonary edema, MPO activity increase, neutrophil infiltration, and respiratory function impairment in a dose-independent manner. However, LPS-induced hypothermia dynamics and duration were dose-dependent. The inhibitory effects of the reference compound dexamethasone were only detectable in the case of the 0.25 mg/kg LPS dose on most inflammatory parameters. These results did not differ substantially between C57BL/6J and NMRI mouse strains. <b>Conclusions</b>: Very low doses of LPS induce characteristic functional and morphological inflammatory alterations in the lung, which do not worsen in response to even 20 times higher doses. Since the effect of pharmacological interventions is likely to be detectable in the case of the 0.25 mg/kg LPS dose, we suggest this protocol for testing novel anti-inflammatory agents.https://www.mdpi.com/2227-9059/13/6/1498acute lung injuryLPSdexamethasoneC57BL/6JNMRIairway function |
| spellingShingle | Emese Ritter Kitti Hohl László Kereskai Ágnes Kemény Dóra Hargitai Veronika Szombati Anikó Perkecz Eszter Pakai Andras Garami Ákos Zsembery Zsuzsanna Helyes Kata Csekő Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model Biomedicines acute lung injury LPS dexamethasone C57BL/6J NMRI airway function |
| title | Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model |
| title_full | Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model |
| title_fullStr | Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model |
| title_full_unstemmed | Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model |
| title_short | Optimization, Characterization and Pharmacological Validation of the Endotoxin-Induced Acute Pneumonitis Mouse Model |
| title_sort | optimization characterization and pharmacological validation of the endotoxin induced acute pneumonitis mouse model |
| topic | acute lung injury LPS dexamethasone C57BL/6J NMRI airway function |
| url | https://www.mdpi.com/2227-9059/13/6/1498 |
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