Olodaterol attenuates bleomycin induced lung fibrosis in mice
| Autor: | Florian Gantner, Stefan-Lutz Wollin, Franziska Herrmann, Eva Wex |
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| Rok vydání: | 2016 |
| Předmět: |
Agonist
Vital capacity medicine.diagnostic_test business.industry medicine.drug_class Olodaterol respiratory system Pharmacology Bleomycin respiratory tract diseases chemistry.chemical_compound FEV1/FVC ratio medicine.anatomical_structure Bronchoalveolar lavage chemistry In vivo White blood cell Immunology Medicine business |
| Zdroj: | 5.1 Airway Pharmacology and Treatment. |
| Popis: | Background: The long-acting β 2 -agonist (LABA) olodaterol was shown to have anti-fibrotic activity in primary human lung fibroblasts (Herrmann et al, Eur Respir J. 2014;44:Suppl.58) however, its anti-fibrotic in vivo efficacy has not yet been demonstrated. Aim: To test the effect of olodaterol in a mouse model of bleomycin induced lung fibrosis. Methods: Bleomycin at a dose of 0.5 mg/kg (1.5-2 U/mg) was intratracheally instilled in C57BL/6 mice on day 0. In a preventive (day 1-20) or therapeutic (day 7 -20) treatment regimen mice were exposed once daily for 5 min to an aqueous solution of olodaterol (1 mg/mL) aerosolized with a jet nebulizer. At the end of the study (day 21) lung density was assessed by micro CT analysis and lung function was measured with a FlexiVent system. Bronchoalveolar lavage fluid (BALF) was analyzed for total and differential cell counts and pro-fibrotic cytokines. Results: The bleomycin challenge induced an increase in lung tissue density, white blood cell (WBC) count and protein concentration in the BAL fluid and a decrease in forced vital capacity (FVC). In the preventive treatment regimen olodaterol attenuated tissue density by 45%, WBC count by 31%, protein by 63% and FVC by 57%. Pro-fibrotic cytokines like TGF-s or MMP-9 were diminished by 57% and 48%, respectively. Therapeutic treatment with olodaterol attenuated the increase in lung density and the decrease in FVC by 10% and 18%, respectively. WBC accumulation was attenuated by 25% and the increase in total protein, TGF-s and MMP-9 levels in BALF was inhibited by 43%, 58% and 49%, respectively. Conclusion: At doses of maximal bronchodilation, olodaterol showed anti-fibrotic properties in a mouse model of bleomycin induced lung fibrosis. |
| Databáze: | OpenAIRE |
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